Longitudinal analysis of FcRL5 expression and clonal relationships among classical and atypical memory B cells following malaria

Malaria Journal

Bryan Greenhouse¹  Richard Sullivan²  S. Jake Gonzales³  Evelien M. Bunnik³  Sebastiaan Bol³  Ashley E. Braddom³  Raphael A. Reyes³  Erica Eggers⁴  Isaac Ssewanyana⁵ 

[1] Department of Medicine, University of California San Francisco, San Francisco, CA, USA;Department of Medicine, University of California San Francisco, San Francisco, CA, USA;Shape Therapeutics, 219 Terry St., Seattle, WA, USA;Department of Microbiology, Immunology and Molecular Genetics, Long School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA;Department of Neurology, UCSF Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA;London School of Hygiene and Tropical Medicine, London, UK;Infectious Disease Research Collaboration, Kampala, Uganda;

关键词: Plasmodium falciparum;    Adaptive immune response;    Humoral immunity;    B cell differentiation;    Infection;    BCR-sequencing;    B cell receptor;   

DOI  :  10.1186/s12936-021-03970-1

来源: Springer

【 摘 要 】

BackgroundChronic and frequently recurring infectious diseases, such as malaria, are associated with expanded populations of atypical memory B cells (MBCs). These cells are different from classical MBCs by the lack of surface markers CD21 and CD27 and increased expression of inhibitory receptors, such as FcRL5. While the phenotype and conditions leading to neogenesis of atypical MBCs in malaria-experienced individuals have been studied extensively, the origin of these cells remains equivocal. Functional similarities between FcRL5+ atypical MBCs and FcRL5+ classical MBCs have been reported, suggesting that these cells may be developmentally related.MethodsHere, a longitudinal analysis of FcRL5 expression in various B cell subsets was performed in two children from a high transmission region in Uganda over a 6-month period in which both children experienced a malaria episode. Using B-cell receptor (BCR)-sequencing to track clonally related cells, the connections between IgM+ and IgG+ atypical MBCs and other B cell subsets were studied.ResultsThe highest expression of FcRL5 was found among IgG+ atypical MBCs, but FcRL5+ cells were present in all MBC subsets. Following malaria, FcRL5 expression increased in all IgM+ MBC subsets analysed here: classical, activated, and atypical MBCs, while results for IgG+ MBC subsets were inconclusive. IgM+ atypical MBCs showed few connections with other B cell subsets, higher turnover than IgG+ atypical MBCs, and were predominantly derived from naïve B cells and FcRL5− IgM+ classical MBCs. In contrast, IgG+ atypical MBCs were clonally expanded and connected with classical MBCs. IgG+ atypical MBCs present after a malaria episode mainly originated from FcRL5+ IgG+ classical MBCs.ConclusionsCollectively, these results suggest fundamental differences between unswitched and class-switched B cell populations and provide clues about the primary developmental pathways of atypical MBCs in malaria-experienced individuals.

【 授权许可】

CC BY