The role of polyreactive memory B cells in systemic lupus erythematosus

In systemic lupus erythematosus (SLE), the production of autoantibodies is a crucial characteristic, and B cells play a significant role in its pathogenesis. B cells are the immune cells most associated with the genetic predispositions of SLE, and recent clinical studies showing that anti-CD19 chimeric antigen receptor (CAR)-T cell therapy induces drug-free remission have underscored the importance of B cells in SLE. Meanwhile, various B-cell subsets exist across different stages of differentiation, from naive B cells to plasma cells, and identifying the important subpopulations within SLE remains a critical future challenge. Years of B-cell repertoire analyses have revealed the importance of polyreactive B-cell receptors (BCRs) and autoantibodies that react to various self-antigens and microbial antigens. Particularly, memory B cells with polyreactive BCRs, which play a crucial role in biological defense during the fetal stage, are characteristically differentiated in SLE. Type I interferon-mediated expression of CXCL13 and IL-21 in CD4+ T cells is associated with the development of polyreactive memory B cells. The expansion of the polyreactive B-cell repertoire, vital for defending against infections such as viruses, may exert an intrinsic function in SLE.