Levels of autoantibodies, unlike antibodies to all extrinsic antigen groups, fall following B cell depletion with Rituximab

Many autoantibodies have variable-region sequences indicating their production in an affinity-matured antibody response involving germinal centers (GC). Plasma cells from GC can be long-lived, do not express CD20 and thus should not be depleted by a therapeutic monoclonal Ab against human CD20 - Rituximab. Nevertheless, autoantibody titers often fall following Rituximab treatment. To test if this reflects exclusive production by short-lived plasma cells in extrafollicular Ab responses, we monitored, after Rituximab treatment, levels of natural Ab and Ab against extrinsic antigens that do not induce productive GC. Eleven patients with active vasculitis and anti-proteinase-3 (PR3) Ab were assessed before and during 5 months after Rituximab therapy. Blood B cells were undetectable within 2 wk, and all patients achieved clinical remission. Levels of natural Ab - isohemagglutinins and anti-phosphorylcholine Ab - and Ab levels against thymus-independent and thymus-dependent extrinsic antigens were little affected. By contrast, 5 months after Rituximab, IgG autoantibody against PR3 had fallen to a median of 22% of pretreatment values. While the kinetics of this fall do not suggest an intrinsically short lifespan of autoantibody-producing cells, the data are consistent with Rituximab causing loss of sites within inflammatory tissues that selectively sustain autoantibody-producing cells.