In:
Journal of Experimental Medicine, Rockefeller University Press, Vol. 220, No. 5 ( 2023-05-01)
Abstract:
Age-associated B cells (ABCs) are formed under inflammatory conditions and are considered a type of memory B cell (MBC) expressing the transcription factor T-bet. In SLE, ABC frequency is correlated with disease, and they are thought to be the source of autoantibody-secreting cells. However, in inflammatory conditions, whether autoreactive B cells can become resting MBCs is uncertain. Further, the phenotypic identity of ABCs and their relationship to other B cell subsets, such as plasmablasts, is unclear. Whether ABCs directly promote disease is untested. Here we report, in the MRL/lpr SLE model, unexpected heterogeneity among ABC-like cells for expression of the integrins CD11b and CD11c, T-bet, and memory or plasmablast markers. Transfer and labeling studies demonstrated that ABCs are dynamic, rapidly turning over. scRNA-seq identified B cell clones present in multiple subsets, revealing that ABCs can be plasmablast precursors or undergo cycles of reactivation. Deletion of CD11c-expressing B cells revealed a direct role for ABC-like B cells in lupus pathogenesis.
Type of Medium:
Online Resource
ISSN:
0022-1007
,
1540-9538
DOI:
10.1084/jem.20221346
Language:
English
Publisher:
Rockefeller University Press
Publication Date:
2023
detail.hit.zdb_id:
1477240-1