Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond

BMC Immunology

Yolande Richard²  Fabrice Cognasse¹  Bruno Pozzetto³  Séverine Degrelle²  Gamal Badr⁴  Gwenoline Borhis²  Olivier Garraud⁵ 

[1] EFS Auvergne-Loire, Saint-Etienne, France;Université Paris Descartes, Sorbonne Paris Cité, Paris, France;Laboratoire de Microbiologie et Hygiène, CHU de Saint-Etienne, Saint-Etienne, France;Princes Johara Alibrahim Center for Cancer Research, Prostate Cancer Research Chair, College of Medicine, King Saud University, Riyadh, Saudi Arabia;Vice-Rectorate for Graduate Studies and Research-Visiting Professor Program, King Saud University, Riyadh, Saudi Arabia

关键词: Chemokines;    Cytokines;    TLR;    B-cells;    Breg;    MZ;    BcR;   

Others  :  1077864
DOI  :  10.1186/1471-2172-13-63

 received in 2012-07-25, accepted in 2012-11-05,  发布年份 2012

【 摘 要 】

The immunological roles of B-cells are being revealed as increasingly complex by functions that are largely beyond their commitment to differentiate into plasma cells and produce antibodies, the key molecular protagonists of innate immunity, and also by their compartmentalisation, a more recently acknowledged property of this immune cell category. For decades, B-cells have been recognised by their expression of an immunoglobulin that serves the function of an antigen receptor, which mediates intracellular signalling assisted by companion molecules. As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating. Since the discovery that the B-cell family included two distinct categories — the non-conventional, or extrafollicular, B1 cells, that have mainly been characterised in the mouse; and the conventional, or lymph node type, B2 cells — plus the detailed description of the main B-cell regulator, FcγRIIb, and the function of CD40⁺ antigen presenting cells as committed/memory B-cells, progress in B-cell physiology has been slower than in other areas of immunology. Cellular and molecular tools have enabled the revival of innate immunity by allowing almost all aspects of cellular immunology to be re-visited. As such, B-cells were found to express “Pathogen Recognition Receptors” such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity. An era of B-cell phenotypic and functional analysis thus began that encompassed the study of B-cell microanatomy principally in the lymph nodes, spleen and mucosae. The novel discovery of the differential localisation of B-cells with distinct phenotypes and functions revealed the compartmentalisation of B-cells. This review thus aims to describe novel findings regarding the B-cell compartments found in the mouse as a model organism, and in human physiology and pathology. It must be emphasised that some differences are noticeable between the mouse and human systems, thus increasing the complexity of B-cell compartmentalisation. Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology.

【 授权许可】

   
2012 Garraud et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Chaganti S, Heath EM, Bergler W, Kuo M, Buettner M, Niedobitek G, Rickinson AB, Bell AI: Epstein-Barr virus colonization of tonsillar and peripheral blood B-cell subsets in primary infection and persistence. Blood 2009, 113(25):6372-6381.
• [2]Zhu Y, Yao S, Chen L: Cell surface signaling molecules in the control of immune responses: a tide model. Immunity 2011, 34(4):466-478.
• [3]Al-Daccak R, Mooney N, Charron D: MHC class II signaling in antigen-presenting cells. Curr Opin Immunol 2004, 16(1):108-113.
• [4]Cognasse F, Payrat JM, Corash L, Osselaer JC, Garraud O: Platelet components associated with acute transfusion reactions: the role of platelet-derived soluble CD40 ligand. Blood 2008, 112(12):4779-4780.
• [5]Zouali M: B lymphocytes–chief players and therapeutic targets in autoimmune diseases. Front Biosci 2008, 13:4852-4861.
• [6]Beutler BA: TLRs and innate immunity. Blood 2009, 113(7):1399-1407.
• [7]Bourke E, Bosisio D, Golay J, Polentarutti N, Mantovani A: The toll-like receptor repertoire of human B lymphocytes: inducible and selective expression of TLR9 and TLR10 in normal and transformed cells. Blood 2003, 102(3):956-963.
• [8]Peng SL: Signaling in B cells via Toll-like receptors. Curr Opin Immunol 2005, 17(3):230-236.
• [9]Fillatreau S, Manz RA: Tolls for B cells. Eur J Immunol 2006, 36(4):798-801.
• [10]Cognasse F, Hamzeh-Cognasse H, Lafarge S, Chavarin P, Pozzetto B, Richard Y, Garraud O: Identification of two subpopulations of purified human blood B cells, CD27- CD23+ and CD27high CD80+, that strongly express cell surface Toll-like receptor 9 and secrete high levels of interleukin-6. Immunology 2008, 125(3):430-437.
• [11]Isnardi I, Ng YS, Menard L, Meyers G, Saadoun D, Srdanovic I, Samuels J, Berman J, Buckner JH, Cunningham-Rundles C, et al.: Complement receptor 2/CD21- human naive B cells contain mostly autoreactive unresponsive clones. Blood 2010, 115(24):5026-5036.
• [12]Richard Y, Amiel C, Jeantils V, Mestivier D, Portier A, Dhello G, Feuillard J, Creidy R, Nicolas JC, Raphael M: Changes in blood B cell phenotypes and Epstein-Barr virus load in chronically human immunodeficiency virus-infected patients before and after antiretroviral therapy. J Infect Dis 2010, 202(9):1424-1434.
• [13]Ng VL, McGrath MS: The immunology of AIDS-associated lymphomas. Immunol Rev 1998, 162:293-298.
• [14]Melchers F, Rolink AG, Schaniel C: The role of chemokines in regulating cell migration during humoral immune responses. Cell 1999, 99(4):351-354.
• [15]Bowman EP, Campbell JJ, Soler D, Dong Z, Manlongat N, Picarella D, Hardy RR, Butcher EC: Developmental switches in chemokine response profiles during B cell differentiation and maturation. J Exp Med 2000, 191(8):1303-1318.
• [16]Hargreaves DC, Hyman PL, Lu TT, Ngo VN, Bidgol A, Suzuki G, Zou YR, Littman DR, Cyster JG: A coordinated change in chemokine responsiveness guides plasma cell movements. J Exp Med 2001, 194(1):45-56.
• [17]Forster R, Mattis AE, Kremmer E, Wolf E, Brem G, Lipp M: A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen. Cell 1996, 87(6):1037-1047.
• [18]Krzysiek R, Lefevre EA, Bernard J, Foussat A, Galanaud P, Louache F, Richard Y: Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha/CCL20 in human B cells. Blood 2000, 96(7):2338-2345.
• [19]Lamm ME, Phillips-Quagliata JM: Origin and homing of intestinal IgA antibody-secreting cells. J Exp Med 2002, 195(2):F5-8.
• [20]Lazarus NH, Kunkel EJ, Johnston B, Wilson E, Youngman KR, Butcher EC: A common mucosal chemokine (mucosae-associated epithelial chemokine/CCL28) selectively attracts IgA plasmablasts. J Immunol 2003, 170(7):3799-3805.
• [21]Casamayor-Palleja M, Mondiere P, Amara A, Bella C, Dieu-Nosjean MC, Caux C, Defrance T: Expression of macrophage inflammatory protein-3alpha, stromal cell-derived factor-1, and B-cell-attracting chemokine-1 identifies the tonsil crypt as an attractive site for B cells. Blood 2001, 97(12):3992-3994.
• [22]McDonnell M, Liang Y, Noronha A, Coukos J, Kasper DL, Farraye FA, Ganley-Leal LM: Systemic Toll-like receptor ligands modify B-cell responses in human inflammatory bowel disease. Inflamm Bowel Dis 2011, 17(1):298-307.
• [23]Liang Y, Hasturk H, Elliot J, Noronha A, Liu X, Wetzler LM, Massari P, Kantarci A, Winter HS, Farraye FA, et al.: Toll-like receptor 2 induces mucosal homing receptor expression and IgA production by human B cells. Clin Immunol 2011, 138(1):33-40.
• [24]Viau M, Longo NS, Lipsky PE, Zouali M: Staphylococcal protein a deletes B-1a and marginal zone B lymphocytes expressing human immunoglobulins: an immune evasion mechanism. J Immunol 2005, 175(11):7719-7727.
• [25]Kearney JF: B cell subpopulations and secondary lymphoid organ architecture. Semin Immunol 2008, 20(1):1-3.
• [26]Hsu MC, Toellner KM, Vinuesa CG, Maclennan IC: B cell clones that sustain long-term plasmablast growth in T-independent extrafollicular antibody responses. Proc Natl Acad Sci USA 2006, 103(15):5905-5910.
• [27]Kraal G: Cells in the marginal zone of the spleen. Int Rev Cytol 1992, 132:31-74.
• [28]Koike R, Nishimura T, Yasumizu R, Tanaka H, Hataba Y, Hataba Y, Watanabe T, Miyawaki S, Miyasaka M: The splenic marginal zone is absent in alymphoplastic aly mutant mice. Eur J Immunol 1996, 26(3):669-675.
• [29]Nolte MA, Arens R, Kraus M, van Oers MH, Kraal G, van Lier RA, Mebius RE: B cells are crucial for both development and maintenance of the splenic marginal zone. J Immunol 2004, 172(6):3620-3627.
• [30]Backer R, Schwandt T, Greuter M, Oosting M, Jungerkes F, Tuting T, Boon L, O'Toole T, Kraal G, Limmer A, et al.: Effective collaboration between marginal metallophilic macrophages and CD8+ dendritic cells in the generation of cytotoxic T cells. Proc Natl Acad Sci USA 2011, 107(1):216-221.
• [31]Odermatt B, Eppler M, Leist TP, Hengartner H, Zinkernagel RM: Virus-triggered acquired immunodeficiency by cytotoxic T-cell-dependent destruction of antigen-presenting cells and lymph follicle structure. Proc Natl Acad Sci USA 1991, 88(18):8252-8256.
• [32]Aichele P, Zinke J, Grode L, Schwendener RA, Kaufmann SH, Seiler P: Macrophages of the splenic marginal zone are essential for trapping of blood-borne particulate antigen but dispensable for induction of specific T cell responses. J Immunol 2003, 171(3):1148-1155.
• [33]Yokota T, Ehlin-Henriksson B, Hansson GK: Scavenger receptors mediate adhesion of activated B lymphocytes. Exp Cell Res 1998, 239(1):16-22.
• [34]Chen Y, Pikkarainen T, Elomaa O, Soininen R, Kodama T, Kraal G, Tryggvason K: Defective microarchitecture of the spleen marginal zone and impaired response to a thymus-independent type 2 antigen in mice lacking scavenger receptors MARCO and SR-A. J Immunol 2005, 175(12):8173-8180.
• [35]You Y, Myers RC, Freeberg L, Foote J, Kearney JF, Justement LB, Carter RH: Marginal zone B cells regulate antigen capture by marginal zone macrophages. J Immunol 2011, 186(4):2172-2181.
• [36]Koppel EA, Litjens M, van den Berg VC, van Kooyk Y, Geijtenbeek TB: Interaction of SIGNR1 expressed by marginal zone macrophages with marginal zone B cells is essential to early IgM responses against Streptococcus pneumoniae. Mol Immunol 2008, 45(10):2881-2887.
• [37]You Y, Zhao H, Wang Y, Carter RH: Cutting edge: Primary and secondary effects of CD19 deficiency on cells of the marginal zone. J Immunol 2009, 182(12):7343-7347.
• [38]Eloranta ML, Alm GV: Splenic marginal metallophilic macrophages and marginal zone macrophages are the major interferon-alpha/beta producers in mice upon intravenous challenge with herpes simplex virus. Scand J Immunol 1999, 49(4):391-394.
• [39]Louten J, van Rooijen N, Biron CA: Type 1 IFN deficiency in the absence of normal splenic architecture during lymphocytic choriomeningitis virus infection. J Immunol 2006, 177(5):3266-3272.
• [40]Montoya M, Schiavoni G, Mattei F, Gresser I, Belardelli F, Borrow P, Tough DF: Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood 2002, 99(9):3263-3271.
• [41]Le Bon A, Etchart N, Rossmann C, Ashton M, Hou S, Gewert D, Borrow P, Tough DF: Cross-priming of CD8+ T cells stimulated by virus-induced type I interferon. Nat Immunol 2003, 4(10):1009-1015.
• [42]Timens W: The human spleen and the immune system: not just another lymphoid organ. Res Immunol 1991, 142(4):316-320.
• [43]Timens W, Boes A, Vos H, Poppema S: Tissue distribution of the C3d/EBV-receptor: CD21 monoclonal antibodies reactive with a variety of epithelial cells, medullary thymocytes, and peripheral T-cells. Histochemistry 1991, 95(6):605-611.
• [44]Steiniger B, Timphus EM, Barth PJ: The splenic marginal zone in humans and rodents: an enigmatic compartment and its inhabitants. Histochem Cell Biol 2006, 126(6):641-648.
• [45]Steiniger B, Barth P, Herbst B, Hartnell A, Crocker PR: The species-specific structure of microanatomical compartments in the human spleen: strongly sialoadhesin-positive macrophages occur in the perifollicular zone, but not in the marginal zone. Immunology 1997, 92(2):307-316.
• [46]Steiniger B, Timphus EM, Jacob R, Barth PJ: CD27+ B cells in human lymphatic organs: re-evaluating the splenic marginal zone. Immunology 2005, 116(4):429-442.
• [47]Steiniger B, Barth P, Hellinger A: The perifollicular and marginal zones of the human splenic white pulp: do fibroblasts guide lymphocyte immigration? Am J Pathol 2001, 159(2):501-512.
• [48]Steiniger B, Stachniss V, Schwarzbach H, Barth PJ: Phenotypic differences between red pulp capillary and sinusoidal endothelia help localizing the open splenic circulation in humans. Histochem Cell Biol 2007, 128(5):391-398.
• [49]Pack M, Trumpfheller C, Thomas D, Park CG, Granelli-Piperno A, Munz C, Steinman RM: DEC-205/CD205+ dendritic cells are abundant in the white pulp of the human spleen, including the border region between the red and white pulp. Immunology 2008, 123(3):438-446.
• [50]Nascimbeni M, Perie L, Chorro L, Diocou S, Kreitmann L, Louis S, Garderet L, Fabiani B, Berger A, Schmitz J, et al.: Plasmacytoid dendritic cells accumulate in spleens from chronically HIV-infected patients but barely participate in interferon-alpha expression. Blood 2009, 113(24):6112-6119.
• [51]Crowley MT, Reilly CR, Lo D: Influence of lymphocytes on the presence and organization of dendritic cell subsets in the spleen. J Immunol 1999, 163(9):4894-4900.
• [52]Birjandi SZ, Ippolito JA, Ramadorai AK, Witte PL: Alterations in marginal zone macrophages and marginal zone B cells in old mice. J Immunol 2011, 186(6):3441-3451.
• [53]Zindl CL, Kim TH, Zeng M, Archambault AS, Grayson MH, Choi K, Schreiber RD, Chaplin DD: The lymphotoxin LTalpha(1)beta(2) controls postnatal and adult spleen marginal sinus vascular structure and function. Immunity 2009, 30(3):408-420.
• [54]Moseman EA, Iannacone M, Bosurgi L, Tonti E, Chevrier N, Tumanov A, Fu YX, Hacohen N, von Andrian UH: B cell maintenance of subcapsular sinus macrophages protects against a fatal viral infection independent of adaptive immunity. Immunity 2012, 36(3):415-426.
• [55]Lu TT, Cyster JG: Integrin-mediated long-term B cell retention in the splenic marginal zone. Science 2002, 297(5580):409-412.
• [56]Cinamon G, Zachariah MA, Lam OM, Foss FW Jr, Cyster JG: Follicular shuttling of marginal zone B cells facilitates antigen transport. Nat Immunol 2008, 9(1):54-62.
• [57]Ato M, Nakano H, Kakiuchi T, Kaye PM: Localization of marginal zone macrophages is regulated by C-C chemokine ligands 21/19. J Immunol 2004, 173(8):4815-4820.
• [58]Girkontaite I, Sakk V, Wagner M, Borggrefe T, Tedford K, Chun J, Fischer KD: The sphingosine-1-phosphate (S1P) lysophospholipid receptor S1P3 regulates MAdCAM-1+ endothelial cells in splenic marginal sinus organization. J Exp Med 2004, 200(11):1491-1501.
• [59]Cinamon G, Matloubian M, Lesneski MJ, Xu Y, Low C, Lu T, Proia RL, Cyster JG: Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone. Nat Immunol 2004, 5(7):713-720.
• [60]Engwerda CR, Ato M, Cotterell SE, Mynott TL, Tschannerl A, Gorak-Stolinska PM, Kaye PM: A role for tumor necrosis factor-alpha in remodeling the splenic marginal zone during Leishmania donovani infection. Am J Pathol 2002, 161(2):429-437.
• [61]Saito T, Chiba S, Ichikawa M, Kunisato A, Asai T, Shimizu K, Yamaguchi T, Yamamoto G, Seo S, Kumano K, et al.: Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development. Immunity 2003, 18(5):675-685.
• [62]Hozumi K, Negishi N, Suzuki D, Abe N, Sotomaru Y, Tamaoki N, Mailhos C, Ish-Horowicz D, Habu S, Owen MJ: Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo. Nat Immunol 2004, 5(6):638-644.
• [63]Khan WN, Alt FW, Gerstein RM, Malynn BA, Larsson I, Rathbun G, Davidson L, Muller S, Kantor AB, Herzenberg LA, et al.: Defective B cell development and function in Btk-deficient mice. Immunity 1995, 3(3):283-299.
• [64]Tanigaki K, Han H, Yamamoto N, Tashiro K, Ikegawa M, Kuroda K, Suzuki A, Nakano T, Honjo T: Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells. Nat Immunol 2002, 3(5):443-450.
• [65]Loder F, Mutschler B, Ray RJ, Paige CJ, Sideras P, Torres R, Lamers MC, Carsetti R: B cell development in the spleen takes place in discrete steps and is determined by the quality of B cell receptor-derived signals. J Exp Med 1999, 190(1):75-89.
• [66]Pillai S, Cariappa A: The follicular versus marginal zone B lymphocyte cell fate decision. Nat Rev Immunol 2009, 9(11):767-777.
• [67]Dunn-Walters DK, Isaacson PG, Spencer J: Analysis of mutations in immunoglobulin heavy chain variable region genes of microdissected marginal zone (MGZ) B cells suggests that the MGZ of human spleen is a reservoir of memory B cells. J Exp Med 1995, 182(2):559-566.
• [68]Tangye SG, Liu YJ, Aversa G, Phillips JH, de Vries JE: Identification of functional human splenic memory B cells by expression of CD148 and CD27. J Exp Med 1998, 188(9):1691-1703.
• [69]Weller S, Braun MC, Tan BK, Rosenwald A, Cordier C, Conley ME, Plebani A, Kumararatne DS, Bonnet D, Tournilhac O, et al.: Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. Blood 2004, 104(12):3647-3654.
• [70]Rosner K, Winter DB, Tarone RE, Skovgaard GL, Bohr VA, Gearhart PJ: Third complementarity-determining region of mutated VH immunoglobulin genes contains shorter V, D, J, P, and N components than non-mutated genes. Immunology 2001, 103(2):179-187.
• [71]Weller S, Mamani-Matsuda M, Picard C, Cordier C, Lecoeuche D, Gauthier F, Weill JC, Reynaud CA: Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+ IgD+ CD27+ B cell repertoire in infants. J Exp Med 2008, 205(6):1331-1342.
• [72]Weill J, Weller S, Reynaud C: Human Marginal Zone B cells. Annu Rev Immunol 2009, 27:267-285.
• [73]Litinskiy MB, Nardelli B, Hilbert DM, He B, Schaffer A, Casali P, Cerutti A: DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol 2002, 3(9):822-829.
• [74]Willenbrock K, Jungnickel B, Hansmann ML, Kuppers R: Human splenic marginal zone B cells lack expression of activation-induced cytidine deaminase. Eur J Immunol 2005, 35(10):3002-3007.
• [75]Mackay F, Browning JL: BAFF: a fundamental survival factor for B cells. Nat Rev Immunol 2002, 2(7):465-475.
• [76]Lavie F, Miceli-Richard C, Quillard J, Roux S, Leclerc P, Mariette X: Expression of BAFF (BLyS) in T cells infiltrating labial salivary glands from patients with Sjogren's syndrome. J Pathol 2004, 202(4):496-502.
• [77]Mariette X, Roux S, Zhang J, Bengoufa D, Lavie F, Zhou T, Kimberly R: The level of BLyS (BAFF) correlates with the titre of autoantibodies in human Sjogren's syndrome. Ann Rheum Dis 2003, 62(2):168-171.
• [78]Fletcher CA, Sutherland AP, Groom JR, Batten ML, Ng LG, Gommerman J, Mackay F: Development of nephritis but not sialadenitis in autoimmune-prone BAFF transgenic mice lacking marginal zone B cells. Eur J Immunol 2006, 36(9):2504-2514.
• [79]Ittah M, Miceli-Richard C, Gottenberg JE, Sellam J, Eid P, Lebon P, Pallier C, Lepajolec C, Mariette X: Viruses induce high expression of BAFF by salivary gland epithelial cells through TLR- and type-I IFN-dependent and -independent pathways. Eur J Immunol 2008, 38(4):1058-1064.
• [80]Ittah M, Miceli-Richard C, Lebon P, Pallier C, Lepajolec C, Mariette X: Induction of B cell-activating factor by viral infection is a general phenomenon, but the types of viruses and mechanisms depend on cell type. J Innate Immun 2011, 3(2):200-207.
• [81]Chaoul N, Burelout C, Peruchon S, van Buu BN, Laurent P, Proust A, Raphael M, Garraud O, Le Grand R, Prevot S, et al.: Default in plasma and intestinal IgA responses during acute infection by simian immunodeficiency virus. Retrovirology 2012, 9:43. BioMed Central Full Text
• [82]Peruchon S, Chaoul N, Burelout C, Delache B, Brochard P, Laurent P, Cognasse F, Prevot S, Garraud O, Le Grand R, et al.: Tissue-specific B-cell dysfunction and generalized memory B-cell loss during acute SIV infection. PLoS One 2009, 4(6):e5966.
• [83]Ferguson AR, Youd ME, Corley RB: Marginal zone B cells transport and deposit IgM-containing immune complexes onto follicular dendritic cells. Int Immunol 2004, 16(10):1411-1422.
• [84]Shiow LR, Rosen DB, Brdickova N, Xu Y, An J, Lanier LL, Cyster JG, Matloubian M: CD69 acts downstream of interferon-alpha/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 2006, 440(7083):540-544.
• [85]Chang WL, Coro ES, Rau FC, Xiao Y, Erle DJ, Baumgarth N: Influenza virus infection causes global respiratory tract B cell response modulation via innate immune signals. J Immunol 2007, 178(3):1457-1467.
• [86]Badr G, Borhis G, Lefevre EA, Chaoul N, Deshayes F, Dessirier V, Lapree G, Tsapis A, Richard Y: BAFF enhances chemotaxis of primary human B cells: a particular synergy between BAFF and CXCL13 on memory B cells. Blood 2008, 111(5):2744-2754.
• [87]Zandvoort A, Lodewijk ME, de Boer NK, Dammers PM, Kroese FG, Timens W: CD27 expression in the human splenic marginal zone: the infant marginal zone is populated by naive B cells. Tissue Antigens 2001, 58(4):234-242.
• [88]Timens W, Boes A, Rozeboom-Uiterwijk T, Poppema S: Immaturity of the human splenic marginal zone in infancy. Possible contribution to the deficient infant immune response. J Immunol 1989, 143(10):3200-3206.
• [89]Delia D, Cattoretti G, Polli N, Fontanella E, Aiello A, Giardini R, Rilke F, Della Porta G: CD1c but neither CD1a nor CD1b molecules are expressed on normal, activated, and malignant human B cells: identification of a new B-cell subset. Blood 1988, 72(1):241-247.
• [90]Overturf GD: Pneumococcal vaccination of children. Semin Pediatr Infect Dis 2002, 13(3):155-164.
• [91]Giebink GS: The prevention of pneumococcal disease in children. N Engl J Med 2001, 345(16):1177-1183.
• [92]Puga I, Cols M, Barra CM, He B, Cassis L, Gentile M, Comerma L, Chorny A, Shan M, Xu W, et al.: B cell-helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nat Immunol 2012, 13(2):170-180.
• [93]Artz AS, Ershler WB, Longo DL: Pneumococcal vaccination and revaccination of older adults. Clin Microbiol Rev 2003, 16(2):308-318.
• [94]Shi Y, Yamazaki T, Okubo Y, Uehara Y, Sugane K, Agematsu K: Regulation of aged humoral immune defense against pneumococcal bacteria by IgM memory B cell. J Immunol 2005, 175(5):3262-3267.
• [95]Di Sabatino A, Carsetti R, Corazza GR: Post-splenectomy and hyposplenic states. Lancet 2011, 378(9785):86-97.
• [96]Carsetti R, Rosado MM, Wardmann H: Peripheral development of B cells in mouse and man. Immunol Rev 2004, 197:179-191.
• [97]Carsetti R: Characterization of B-cell maturation in the peripheral immune system. Methods Mol Biol 2004, 271:25-35.
• [98]Wong WY, Powars DR, Chan L, Hiti A, Johnson C, Overturf G: Polysaccharide encapsulated bacterial infection in sickle cell anemia: a thirty year epidemiologic experience. Am J Hematol 1992, 39(3):176-182.
• [99]Di Sabatino A, Rosado MM, Ciccocioppo R, Cazzola P, Morera R, Corazza GR, Carsetti R: Depletion of immunoglobulin M memory B cells is associated with splenic hypofunction in inflammatory bowel disease. Am J Gastroenterol 2005, 100(8):1788-1795.
• [100]Di Sabatino A, Rosado MM, Miele L, Capolunghi F, Cazzola P, Biancheri P, Carsetti R, Gasbarrini G, Corazza GR: Impairment of splenic IgM-memory but not switched-memory B cells in a patient with celiac disease and splenic atrophy. J Allergy Clin Immunol 2007, 120(6):1461-1463.
• [101]Spencer J, Finn T, Isaacson PG: Gut associated lymphoid tissue: a morphological and immunocytochemical study of the human appendix. Gut 1985, 26(7):672-679.
• [102]Spencer J: Differentiating ulcerative colitis from Crohn's disease: false dawn for CD44. Gut 1998, 43(3):310-311.
• [103]Spencer J, Perry ME, Dunn-Walters DK: Human marginal-zone B cells. Immunol Today 1998, 19(9):421-426.
• [104]Dono M, Zupo S, Leanza N, Melioli G, Fogli M, Melagrana A, Chiorazzi N, Ferrarini M: Heterogeneity of tonsillar subepithelial B lymphocytes, the splenic marginal zone equivalents. J Immunol 2000, 164(11):5596-5604.
• [105]Kawai T, Akira S: The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 2010, 11(5):373-384.
• [106]Chiron D, Bekeredjian-Ding I, Pellat-Deceunynck C, Bataille R, Jego G: Toll-like receptors: lessons to learn from normal and malignant human B cells. Blood 2008, 112(6):2205-2213.
• [107]Xu W, Santini PA, Matthews AJ, Chiu A, Plebani A, He B, Chen K, Cerutti A: Viral double-stranded RNA triggers Ig class switching by activating upper respiratory mucosa B cells through an innate TLR3 pathway involving BAFF. J Immunol 2008, 181(1):276-287.
• [108]Wetzler LM: The role of Toll-like receptor 2 in microbial disease and immunity. Vaccine 2003, 21(Suppl 2):S55-60.
• [109]Bekeredjian-Ding I, Inamura S, Giese T, Moll H, Endres S, Sing A, Zahringer U, Hartmann G: Staphylococcus aureus protein A triggers T cell-independent B cell proliferation by sensitizing B cells for TLR2 ligands. J Immunol 2007, 178(5):2803-2812.
• [110]Cognasse F, Hamzeh H, Chavarin P, Acquart S, Genin C, Garraud O: Evidence of Toll-like receptor molecules on human platelets. Immunol Cell Biol 2005, 83(2):196-198.
• [111]Park B, Brinkmann MM, Spooner E, Lee CC, Kim YM, Ploegh HL: Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9. Nat Immunol 2008, 9(12):1407-1414.
• [112]Chaturvedi A, Dorward D, Pierce SK: The B cell receptor governs the subcellular location of Toll-like receptor 9 leading to hyperresponses to DNA-containing antigens. Immunity 2008, 28(6):799-809.
• [113]Bernasconi NL, Onai N, Lanzavecchia A: A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells. Blood 2003, 101(11):4500-4504.
• [114]Jiang W, Lederman MM, Harding CV, Rodriguez B, Mohner RJ, Sieg SF: TLR9 stimulation drives naive B cells to proliferate and to attain enhanced antigen presenting function. Eur J Immunol 2007, 37(8):2205-2213.
• [115]Bekeredjian-Ding IB, Wagner M, Hornung V, Giese T, Schnurr M, Endres S, Hartmann G: Plasmacytoid dendritic cells control TLR7 sensitivity of naive B cells via type I IFN. J Immunol 2005, 174(7):4043-4050.
• [116]Barral P, Eckl-Dorna J, Harwood NE, De Santo C, Salio M, Illarionov P, Besra GS, Cerundolo V, Batista FD: B cell receptor-mediated uptake of CD1d-restricted antigen augments antibody responses by recruiting invariant NKT cell help in vivo. Proc Natl Acad Sci USA 2008, 105(24):8345-8350.
• [117]Lang GA, Illarionov PA, Glatman-Freedman A, Besra GS, Lang ML: BCR targeting of biotin-{alpha}-galactosylceramide leads to enhanced presentation on CD1d and requires transport of BCR to CD1d-containing endocytic compartments. Int Immunol 2005, 17(7):899-908.
• [118]Allan LL, Stax AM, Zheng DJ, Chung BK, Kozak FK, Tan R, van den Elzen P: CD1d and CD1c expression in human B cells is regulated by activation and retinoic acid receptor signaling. J Immunol 2011, 186(9):5261-5272.
• [119]Leadbetter EA, Brigl M, Illarionov P, Cohen N, Luteran MC, Pillai S, Besra GS, Brenner MB: NK T cells provide lipid antigen-specific cognate help for B cells. Proc Natl Acad Sci USA 2008, 105(24):8339-8344.
• [120]Allan LL, Hoefl K, Zheng DJ, Chung BK, Kozak FK, Tan R, van den Elzen P: Apolipoprotein-mediated lipid antigen presentation in B cells provides a pathway for innate help by NKT cells. Blood 2009, 114(12):2411-2416.
• [121]Bialecki E, Paget C, Fontaine J, Capron M, Trottein F, Faveeuw C: Role of marginal zone B lymphocytes in invariant NKT cell activation. J Immunol 2009, 182(10):6105-6113.
• [122]Bosma A, Abdel-Gadir A, Isenberg DA, Jury EC, Mauri C: Lipid-antigen presentation by CD1d(+) B cells is essential for the maintenance of invariant natural killer T cells. Immunity 2012, 36(3):477-490.
• [123]Mauri C, Ehrenstein MR: The 'short' history of regulatory B cells. Trends Immunol 2008, 29(1):34-40.
• [124]Fillatreau S, Gray D, Anderton SM: Not always the bad guys: B cells as regulators of autoimmune pathology. Nat Rev Immunol 2008, 8(5):391-397.
• [125]Bouaziz JD, Yanaba K, Tedder TF: Regulatory B cells as inhibitors of immune responses and inflammation. Immunol Rev 2008, 224:201-214.
• [126]Yanaba K, Bouaziz JD, Haas KM, Poe JC, Fujimoto M, Tedder TF: A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses. Immunity 2008, 28(5):639-650.
• [127]Yanaba K, Bouaziz JD, Matsushita T, Magro CM, St Clair EW, Tedder TF: B-lymphocyte contributions to human autoimmune disease. Immunol Rev 2008, 223:284-299.
• [128]Watanabe R, Ishiura N, Nakashima H, Kuwano Y, Okochi H, Tamaki K, Sato S, Tedder TF, Fujimoto M: Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J Immunol 2011, 184(9):4801-4809.
• [129]Ding Q, Yeung M, Camirand G, Zeng Q, Akiba H, Yagita H, Chalasani G, Sayegh MH, Najafian N, Rothstein DM: Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice. J Clin Invest 2011, 121(9):3645-3656.
• [130]Yang M, Sun L, Wang S, Ko KH, Xu H, Zheng BJ, Cao X, Lu L: Novel function of B cell-activating factor in the induction of IL-10-producing regulatory B cells. J Immunol 2010, 184(7):3321-3325.
• [131]Lund FE, Randall TD: Effector and regulatory B cells: modulators of CD4(+) T cell immunity. Nat Rev Immunol 10(4):236-247.
• [132]Bouaziz JD, Calbo S, Maho-Vaillant M, Saussine A, Bagot M, Bensussan A, Musette P: IL-10 produced by activated human B cells regulates CD4(+) T-cell activation in vitro. Eur J Immunol 2010, 40(10):2686-2691.
• [133]Iwata Y, Matsushita T, Horikawa M, Dilillo DJ, Yanaba K, Venturi GM, Szabolcs PM, Bernstein SH, Magro CM, Williams AD, et al.: Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. Blood 2011, 117(2):530-541.
• [134]Blair PA, Norena LY, Flores-Borja F, Rawlings DJ, Isenberg DA, Ehrenstein MR, Mauri C: CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity 32(1):129-140.
• [135]Zouali M, Richard Y: Marginal zone B-cells, a gatekeeper of innate immunity. Front Immunol 2011, 2:63.
• [136]Hartung HP, Kieseier BC: Atacicept: targeting B cells in multiple sclerosis. Ther Adv Neurol Disord 2010, 3(4):205-216.
• [137]Griffin DO, Rothstein TL: Human "orchestrator" CD11b(+) B1 cells spontaneously secrete IL-10 and regulate T cell activity. Mol Med 2012.
• [138]Hao Y, O'Neill P, Naradikian MS, Scholz JL, Cancro MP: A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice. Blood 2011, 118(5):1294-1304.
• [139]Linterman MA, Vinuesa CG: Signals that influence T follicular helper cell differentiation and function. Semin Immunopathol 2010, 32(2):183-196.
• [140]Rubtsov AV, Rubtsova K, Fischer A, Meehan RT, Gillis JZ, Kappler JW, Marrack P: Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c(+) B-cell population is important for the development of autoimmunity. Blood 2011, 118(5):1305-1315.
• [141]Warnatz K, Wehr C, Drager R, Schmidt S, Eibel H, Schlesier M, Peter HH: Expansion of CD19(hi)CD21(lo/neg) B cells in common variable immunodeficiency (CVID) patients with autoimmune cytopenia. Immunobiology 2002, 206(5):502-513.
• [142]Ehrhardt GR, Hsu JT, Gartland L, Leu CM, Zhang S, Davis RS, Cooper MD: Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells. J Exp Med 2005, 202(6):783-791.
• [143]Falini B, Tiacci E, Pucciarini A, Bigerna B, Kurth J, Hatzivassiliou G, Droetto S, Galletti BV, Gambacorta M, Orazi A, et al.: Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT). Blood 2003, 102(10):3684-3692.
• [144]Ehrhardt GR, Hijikata A, Kitamura H, Ohara O, Wang JY, Cooper MD: Discriminating gene expression profiles of memory B cell subpopulations. J Exp Med 2008, 205(8):1807-1817.
• [145]Weiss GE, Crompton PD, Li S, Walsh LA, Moir S, Traore B, Kayentao K, Ongoiba A, Doumbo OK, Pierce SK: Atypical memory B cells are greatly expanded in individuals living in a malaria-endemic area. J Immunol 2009, 183(3):2176-2182.
• [146]Rakhmanov M, Gutenberger S, Keller B, Schlesier M, Peter HH, Warnatz K: CD21low B cells in common variable immunodeficiency do not show defects in receptor editing, but resemble tissue-like memory B cells. Blood 2010, 116(18):3682-3683.
• [147]Sohn HW, Krueger PD, Davis RS, Pierce SK: FcRL4 acts as an adaptive to innate molecular switch dampening BCR signaling and enhancing TLR signaling. Blood 2011, 118(24):6332-6341.
• [148]Moir S, Ho J, Malaspina A, Wang W, DiPoto AC, O'Shea MA, Roby G, Kottilil S, Arthos J, Proschan MA, et al.: Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med 2008, 205(8):1797-1805.
• [149]Kardava L, Moir S, Wang W, Ho J, Buckner CM, Posada JG, O'Shea MA, Roby G, Chen J, Sohn HW, et al.: Attenuation of HIV-associated human B cell exhaustion by siRNA downregulation of inhibitory receptors. J Clin Invest 2011, 121(7):2614-2624.
• [150]Titanji K, Velu V, Chennareddi L, Vijay-Kumar M, Gewirtz AT, Freeman GJ, Amara RR: Acute depletion of activated memory B cells involves the PD-1 pathway in rapidly progressing SIV-infected macaques. J Clin Invest 2010, 120(11):3878-3890.