Crossroads of B cell activation in autoimmunity: rationale of targeting B cells

B cells have historically been considered as not preferentially involved in the immunopathogenesis of inflammatory joint diseases, in particular rheumatoid arthritis (RA), despite the notion that autoantibodies and immune complexes were involved in pathogenesis and served as diagnostic and classification markers. Following initial reports that patients with non-Hodgkin's lymphoma (NHL) and coexisting RA showed improvement in signs and symptoms of RA after anti-CD20 therapy, the role of B cells in autoimmune diseases was reexamined. Potential mechanisms can be inferred from what is known about the role of B cell functions, in particular antigen-experienced memory B cells. Activation of these cells can be dependent on T lymphocytes or independent of them. Once activated, the cells can efficiently act as antigen-presenting cells, can produce inflammatory cytokines, and may alternatively differentiate into antibody-producing plasma cells. These processes contribute to the activation of other immune cells and ultimately to joint destruction in RA. The development and maintenance of RA may be related to both direct and indirect involvement of these B cell-dependent processes. In systemic lupus erythematosus (SLE), the central pathogenic importance of autoimmune B cells is well recognized, based on early recognition of numerous autoantibodies and clinically important immune complexes. Based on the evidence supporting B cell involvement in the pathophysiology of autoimmune diseases, investigations are evaluating the clinical impact of B cell targeted therapies. B cell targeted therapies in human trials include an anti-B lymphocyte stimulator protein agent, belimumab; an anti-CD20 agent, rituximab; and an anti-CD22 antibody, epratuzumab.