Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease

Significance B cell depletion via anti-CD20 monoclonal antibodies is a novel, highly efficient therapy for multiple sclerosis (MS). In a murine MS model, we investigated three mechanistic questions that cannot be addressed in humans. First, we established that a fraction of mature B cells in the spleen is resistant to anti-CD20. Second, we determined that, after cessation of treatment, splenic and bone-marrow B cells reconstitute in parallel, substantially preceding B cell reappearance in blood. Third, we observed that, in a model involving activated B cells, the post–anti-CD20 B cell pool contained an elevated frequency of differentiated, myelin-reactive B cells. Together, our findings reveal mechanisms by which pathogenic B cells may persist in anti-CD20 treatment.