Reconstitution of self-reactive antibody repertoires of autologous plasma IgM in patients with non-Hodgkin's lymphoma following myeloablative therapy

In healthy individuals, natural self-reactive antibody repertoires are rest ricted to a limited subset of autoantigens that is selected early in develo pment and that remains invariant between individuals through aging. In the present study, we addressed the question of whether self-reactive antibody repertoires of plasma IgM change during high-dose chemotherapy (HDCT) with autologous blood stem cell support and whether antibody repertoires generat ed during immune reconstitution are similar to those present under physiolo gical conditions. We followed the development of antibody repertoires in pa tients undergoing HDCT for the treatment of B-cell non-Hodgkin's lymphoma ( NHL). Antibody repertoires were investigated by quantitative immunoblotting on whole tissue extracts as sources of self-antigens and by multiparametri c statistical analysis of the data. We demonstrate that self-reactive antib ody repertoires of plasma IgM of NHL patients prior to HDCT differ from tho se of healthy individuals, that they change during recovery of immune funct ions, and that antibody repertoires similar to those of healthy individuals are generated during immune reconstitution. We conclude that the mechanism s responsible for the selection of self-reactive repertoires of autologous plasma IgM during immune reconstitution after HDCT may follow those present under physiological conditions and that immune reconstitution may include a shift from altered toward normal patterns of self-reactivity. (C) 2000 Ac ademic Press.