Receptor repertoires of murine follicular T helper cells reveal a high clonal overlap in separate lymph nodes in autoimmunity

eLife

Magali Irla¹  Markus Niebuhr²  Kathrin Kalies²  Julia Belde²  Jürgen Westermann²  Christoph M Hammers³  Christoph T Ellebrecht⁴  Anke Fähnrich⁵  Arnauld Serge⁶  Katja Bieber⁷ 

[1] Centre d'Immunologie de Marseille Luminy (CIML), INSERM U1104, Aix-Marseille Université UM2, Marseille, France;Institute for Anatomy, University of Lübeck, Lübeck, Germany;Institute for Anatomy, University of Lübeck, Lübeck, Germany;Department of Dermatology, University of Lübeck, Lübeck, Germany;Institute for Anatomy, University of Lübeck, Lübeck, Germany;Department of Dermatology, University of Pennsylvania, Philadelphia, United States;Institute for Anatomy, University of Lübeck, Lübeck, Germany;Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany;Laboratoire Adhésion et Inflammation, Inserm U1067 CNRS, Aix-Marseille Université, Marseille, France;Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany;

关键词: adaptive immunity;    germinal center reactions;    follicular T helper cells;    T cell antigen;    receptor sequences;    clonal selection;    Mouse;   

DOI  :  10.7554/eLife.70053

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Follicular T helper cells (Tfh) are a specialized subset of CD4 effector T cells that are crucial for germinal center (GC) reactions and for selecting B cells to undergo affinity maturation. Despite this central role for humoral immunity, only few data exist about their clonal distribution when multiple lymphoid organs are exposed to the same antigen (Ag) as it is the case in autoimmunity. Here, we used an autoantibody-mediated disease model of the skin and injected one auto-Ag into the two footpads of the same mouse and analyzed the T cell receptor (TCR)β sequences of Tfh located in GCs of both contralateral draining lymph nodes. We found that over 90% of the dominant GC-Tfh clonotypes were shared in both lymph nodes but only transiently. The initially dominant Tfh clonotypes especially declined after establishment of chronic disease while GC reaction and autoimmune disease continued. Our data demonstrates a dynamic behavior of Tfh clonotypes under autoimmune conditions and emphasizes the importance of the time point for distinguishing auto-Ag-specific Tfh clonotypes from potential bystander activated ones.

【 授权许可】

CC BY