T‐bet‐expressing B cells contribute to the autoreactive plasma cell pool in Lyn‐/‐ mice.

Systemic Lupus Erythematosus (SLE) is characterized by pathogenic autoantibodies against nucleic acid‐containing antigens. Understanding which B‐cell subsets give rise to these autoantibodies may reveal therapeutic approaches for SLE that spare protective responses. Mice lacking the tyrosine kinase Lyn, which limits B and myeloid cell activation, develop lupus‐like autoimmune diseases characterized by increased autoreactive plasma cells (PCs). We used a fate‐mapping strategy to determine the contribution of T‐bet+ B cells, a subset thought to be pathogenic in lupus, to the accumulation of PCs and autoantibodies in Lyn‐/‐ mice. Approximately, 50% of splenic PCs in Lyn‐/‐ mice originated from T‐bet+ cells, a significant increase compared to WT mice. In vitro, splenic PCs derived from T‐bet+ B cells secreted both IgM and IgG anti‐dsDNA antibodies. To determine the role of these cells in autoantibody production in vivo, we prevented T‐bet+ B cells from differentiating into PCs or class switching in Lyn‐/‐ mice. This resulted in a partial reduction in splenic PCs and anti‐dsDNA IgM and complete abrogation of anti‐dsDNA IgG. Thus, T‐bet+ B cells make an important contribution to the autoreactive PC pool in Lyn‐/‐ mice. [ABSTRACT FROM AUTHOR]