Update on rituximab.

R ituximab is a chimeric monoclonal antibody that was developed for the treatment of B cell lymphomas. It is directed against the CD20 cell surface molecule. CD20 is a tetraspan membrane protein that is present only on B cells, and is expressed initially at the immature B cell stage, remaining until the final differentiation into plasma cells. The function of CD20 is not clear, although it may play some role in signalling or in calcium mobilisation. Curiously, mice that were genetically engineered to lack CD20 (CD20 knockout mice) have not shown any clear defects in their B cells. Nevertheless, the specificity of CD20 for the B cell lineage, and its failure to be easily shed or internalised, has made it an excellent target for depletion by monoclonal antibodies. Not only does rituximab kill CD20+ lymphoma cells, but it also substantially depletes normal B cells from the peripheral blood. Tissue depletion also occurs, but is perhaps less profound, and in any case has been little documented in patients. The mechanism of B cell depletion appears to be a combination of FcRc dependent ADCC (antibody dependent cell mediated cytotoxocity), complement mediated lysis, and apoptosis, although the relative contributions of these mechanisms in vivo remains to be determined, In addition, stimulation of the inhibitory FcRcIIB may also play a role in rituximab therapeutic effects.