Complex subsets but redundant clonality after B cells egress from spontaneous germinal centers

Author:

Castrillon Carlos1ORCID,Simoni Lea1,van den Broek Theo1ORCID,van der Poel Cees1,Akama-Garren Elliot H12ORCID,Ma Minghe1ORCID,Carroll Michael C13ORCID

Affiliation:

1. Program in Cellular and Molecular Medicine, Boston Children’s Hospital

2. Harvard-MIT Health Sciences and Technology, Harvard Medical School

3. Department of Pediatrics, Harvard Medical School

Abstract

Affinity matured self-reactive antibodies are found in autoimmune diseases like systemic lupus erythematous. Here, we used fate-mapping reporter mice and single-cell transcriptomics coupled to antibody repertoire analysis to characterize the post-germinal center (GC) B cell compartment in a new mouse model of autoimmunity. Antibody-secreting cells (ASCs) and memory B cells (MemBs) from spontaneous GCs grouped into multiple subclusters. ASCs matured into two terminal clusters, with distinct secretion, antibody repertoire and metabolic profiles. MemBs contained FCRL5+ and CD23+ subsets, with different in vivo localization in the spleen. GC-derived FCRL5+ MemBs share transcriptomic and repertoire properties with atypical B cells found in aging and infection and localize to the marginal zone, suggesting a similar contribution to recall responses. While transcriptomically diverse, ASC and MemB subsets maintained an underlying clonal redundancy. Therefore, self-reactive clones could escape subset-targeting therapy by perpetuation of self-reactivity in distinct subsets.

Funder

National Institutes of Health

H2020 Marie Skłodowska-Curie Actions

Koninklijke Nederlandse Akademie van Wetenschappen

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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