During the 1990s evidence emerged to suggest that B lymphocyte depletion in rheumatoid arthritis (RA) might be of major benefit.

In 1997 the B lympholytic monoclonal anti-CD20 antibody rituximab became available. Significant clinical efficacy has been demonstrated in RA, initially in open studies at University College London and recently in a multicentre randomised controlled trial. Forty RA patients at University College London have now received in total 75 treatment cycles with rituximab (up to 4 individually) alone or in combination with corticosteroid, cyclophosphamide and/or methotrexate. Ongoing immunodynamic studies of these patients have shed light on a number of questions about both the therapeutic potential of B cell targeting, and the pathogenesis of RA.

The effects of B lymphocyte depletion lend increasing support to the idea that both the inflammatory effector mechanism and the underlying immunoregulatory disturbance in RA are driven by autoantibody rather than T cells.