B cells have been implicated as central players in the autoimmune diseases Sjögren's Syndrome (SS), Systemic Lupus Erythematosus (SLE), and Rheumatoid Arthritis (RA). While it has been reported that B cells participate in both immune and autoimmune response through their traditional role of antibody (and auto-antibody) production--B cells are also known to participate, possibly pathologically, through antibody independent functions such as cytokine production and antigen presentation. It has long been reported that B cells are capable of cytokine production; B cells activated through the B cell Receptor (BCR) or Toll-Like Receptors (TLR) produce cytokines such as IL-10, IL-6 and TNFa.
Preliminary data has shown that B cells produce a large and diverse array of cytokines in biologically significant quantities. Further data has shown that B cells can be induced to make pro-inflammatory cytokines (IFNg, IL-12p40, and TNFa) when stimulated by Th1 cells, or cytokines associated with allergic responses (IL-4) when stimulated by Th2 cells. This B / T cell communication indicates potentially complex effector roles when considering cytokine-producing B cells. In mice, IL-10 producing B cells seem to ameliorate symptoms of autoimmune diseases of RA and Inflammatory Bowel Disease. While the observation that B cells are capable of producing a variety of effector cytokines under differing stimulation conditions is tantalizing, a systematic approach to dissect the function of these cytokine producing B cells is necessary to elucidate their effector functions in both health and autoimmune disease. The immuno-modulatory effects of the cytokines produced and the hypothesis that cytokine-producing B cells contribute in both the healthy state as well as the autoimmune conditions of Sjögren's Syndrome, Lupus and Rheumatoid, through systemic inflammatory modulation and target-tissue influences are being evaluated.