Prospects for B-cell-targeted therapy in autoimmune disease

Reasons for targeting B cells in autoimmune disease date back to the discovery of autoantibodies over 50yr ago [1]. The idea became of practical interest when anti-B cell monoclonal antibodies were developed in the early 1990s [ 2, 3]. Fortuitously, at about the same time it became clear that B cells are not simply the subordinate foot soldiers of an immune response but may be as important as T cells in its genesis and regulation. Moreover, it seemed possible that B cells might actually be the driving force behind human autoimmunity. The concept of therapeutic B-lymphocyte depletion (BLyD) emerged subsequently in the pages of this journal [ 4]. Concept was transformed into reality with the use of the anti-CD20 ( i. e. anti-B cell) monoclonal antibody rituximab [5 -19]. BLyD has provided clear evidence that B-cell targeting has therapeutic potential [ 5-19]. The evidence is most firmly established in rheumatoid arthritis (RA) [ 8] and much of the discussion below will focus on the use of BLyD in RA as a model for other autoimmune conditions. Nevertheless, it is important to consider B- cell targeting on a wider front, and how its application may be different for different disorders.