B cell expressing anti-phospholipase A2 receptor (PLA2R) autoantibodies (Anti-PLA2R+ B cell)

B cells expressing anti-phospholipase A2 receptor (PLA2R) autoantibodies are the central pathogenic drivers of primary membranous nephropathy (PMN), an autoimmune kidney disease (Beck et al., 2009, NEJM). These specialized B lymphocytes lose self-tolerance and produce IgG4 autoantibodies that target the M-type phospholipase A2 receptor (PLA2R1) expressed on glomerular podocytes. The binding of these antibodies results in the formation of subepithelial immune complexes, which trigger complement activation and subsequent podocyte injury, leading to nephrotic-range proteinuria (Hoxha et al., 2014, JASN). Therapeutic strategies for PMN focus on the depletion of these B-cell populations to halt the production of autoantibodies. While current standard-of-care treatments like rituximab target the broader CD20+ B-cell population, research into precision therapies like Chimeric Autoantibody Receptor (CAAR) T cells aims to selectively eliminate only the PLA2R-reactive B cells (Ellebrecht et al., 2016, Science). Serum anti-PLA2R antibody titers serve as a critical biomarker for diagnosing PMN, monitoring disease activity, and predicting clinical relapse (Cattran & Brenchley, 2017, Kidney Int).

Other names

PLA2R-specific B cellAnti-PLA2R antibody-producing B cellPLA2R-reactive B lymphocyteAnti-PLA2R autoantibody-secreting cell

Depletion of B-cell populations or selective elimination of antigen-specific B cells to reduce the production of pathogenic anti-PLA2R autoantibodies.