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

Autor:	Castrillon C; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, United States., Simoni L; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, United States., van den Broek T; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, United States., van der Poel C; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, United States., Akama-Garren EH; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, United States.; Harvard-MIT Health Sciences and Technology, Harvard Medical School, Boston, United States., Ma M; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, United States., Carroll MC; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, United States.; Department of Pediatrics, Harvard Medical School, Boston, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2023 Jun 21; Vol. 12. Date of Electronic Publication: 2023 Jun 21.
DOI:	10.7554/eLife.81012
Abstrakt:	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. Competing Interests: CC, LS, Tv, Cv, EA, MM, MC No competing interests declared (© 2023, Castrillon et al.)
Databáze:	MEDLINE
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