Age-associated B cells are heterogeneous and dynamic drivers of autoimmunity in mice

• Published in: The Journal of experimental medicine Vol. 220; no. 5
• Main Authors: Nickerson, Kevin M., Smita, Shuchi, Hoehn, Kenneth B., Marinov, Anthony D., Thomas, Kayla B., Kos, Justin T., Yang, Yi, Bastacky, Sheldon I., Watson, Corey T., Kleinstein, Steven H., Shlomchik, Mark J.
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 01.05.2023
• Subjects: Animals; Autoimmunity; B-Lymphocyte Subsets; B-Lymphocytes; Lupus Erythematosus, Systemic - metabolism; Mice; Mice, Inbred MRL lpr
• ISSN: 0022-1007; 1540-9538; 1540-9538
• DOI: 10.1084/jem.20221346

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.