B cell reconstitution after rituximab treatment of lymphoma recapitulates B cell ontogeny.

The long-term immunologic effects of B cell depletion with rituximab and the characteristics of the reconstituting B cell pool in lymphoma patients are not well defined, despite the widespread usage of this therapy. Here we report that during the B cell reconstitution phase a majority of the peripheral blood B cells have an immature transitional phenotype (47.8%+/-25.2% vs. 4.4%+/-2.4% for normal controls, p<0.0001), similar to what has been described during the original ontogeny of the immune system and following bone marrow transplantation. Moreover, the recovery of the CD27+ memory B cell pool was delayed compared to normal B cell ontogeny, remaining below normal controls at 1 year post-rituximab (4.4%+/-3% vs. 31%+/-7%, p<0.0001). Expansion of functionally immature B cells and decreased memory B cells may contribute to an immunodeficient state in patients recovering from rituximab mediated B cell depletion, particularly with repeated treatment.