B cell participation in RA. Illustrated is the potential role of B cells in the regulation of immune responses in RA. Mature B cells, upon antigen encounter and TLR stimulation, expand and differentiate into short-lived plasma cells or can enter into a GC reaction, which is necessary for the generation of both memory B cells, and long-lived plasma cells that can produce autoantibodies. Autoantibodies form immune complexes that further activate the immune system via Fc and complement receptors expressed on target cells. Antigen-activated mature B cells provide help to T cells and induce differentiation of effector T cells that produce proinflammatory cytokines (known to be directly/indirectly involved in cartilage and bone destruction). Mature B cells, via mechanisms yet to be elucidated, can also differentiate into IL-10 producing B cells that can dampen the autoreactive T-cell response. GC, germinal centre; IFN, interferon; IL, interleukin; RA, rheumatoid arthritis; TLR, Toll-like receptor ligand; TNF, tumour necrosis factor.