[BCMA and autoantibody-producing RP105 B cells; possible new targets of B cell therapy in systemic lupus erythematosus]

Abstract

Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease with multiple organ disorders. Although the prognosis of SLE has been recently improved, corticosteroid and immunosuppressive agents are still main treatment used in medical practice. Refractory disease and complications by the conventional drugs still remain. RP105 (CD180) is one of the toll-like receptor associated molecules. The molecule is expressed on mature B cells. Significantly increased population of RP105-negative [RP105(-)] B cells is found in SLE. RP105(-) B cells belong to highly activated and differentiated late B cells and produce autoantibodies including anti-dsDNA antibodies. RP105(-) B cells are further divided into at least 5 subsets that include novel human B cell subsets. In active SLE, subset 1 (activated B cells) and 3 (early-plasmablasts) are significantly increased compared to inactive SLE patients. Especially, subset 3 RP105(-) B cells may play an important role in pathophysiology of SLE. RP105(-) B cells from active SLE patients express preferentially BCMA (B-cell maturation antigen) compared to BAFF-R (B-cell activating factor-receptor) than normal subjects and other autoimmune diseases. In SLE, it is suggested that BAFF/APRIL (a proliferation-inducing ligand) maintain chronic activation and survival of RP105(-) B cells. The increased RP105(-) B cells may reflect the breaking of tolerance checkpoint for autoreactive B cells and finally affect autoimmunity in SLE. For the B cell therapy, especially targeting of autoantibody-producing B cells, including subset 3 of RP105(-) B cells, BCMA and RP105(-) B cell itself may be an ideal target.