Complex subsets but redundant clonality after B cells egress from spontaneous germinal centers
- Boston Children's Hospital, United States
- Harvard University, United States
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.
Data availability
The sequencing data presented in this study have been submitted to the Gene Expression Omnibus under accession number GSE203132(https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE203132).
Article and author information
Author details
Theo van den Broek
Elliot H Akama-Garren
Funding
National Institutes of Health (R01AI130307)
- Michael C Carroll
National Institutes of Health (R01AR074105)
- Michael C Carroll
National Institutes of Health (T32GM007753)
- Elliot H Akama-Garren
National Institutes of Health (T32AI007529)
- Elliot H Akama-Garren
National Institutes of Health (F30AI160909)
- Elliot H Akama-Garren
H2020 Marie Skłodowska-Curie Actions (BEAT (No. 796988))
- Theo van den Broek
Academy Ter Meulen Fund (TMB/16/285)
- Theo van den Broek
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All mice were bred and maintained in the AAALAC- accredited facility at Harvard Medical School. Mice were specific pathogen-free (SPF) and maintained under a 12 hr light/dark cycle with standard chow diet. Both male and female mice were used. All animal experiments were conducted in accordance with the guidelines of the Laboratory Animal Center of National Institutes of Health. The Institutional Animal Care and Use Committee of Harvard Medical School approved all animal protocols (protocol number IS111)
Copyright
© 2023, Castrillon et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Complex subsets but redundant clonality after B cells egress from spontaneous germinal centers
eLife 12:e81012.
https://doi.org/10.7554/eLife.81012
