Long-term persistence of oligoclonal serum IgM repertoires in patients treated with allogeneic bone marrow transplantation (BMT)

Immunoglobulin gene rearrangements in patients treated with BMT have restri cted repertoire diversity. Clonal variability remains low for 3 months and reconstitution of the humoral immune system appears to follow a wave-like p attern. In the present study we analysed serum IgM and IgG repertoires in 4 4 patients from 1 week to 3 years after transplantation. We applied a quant itative immunoblot technique in combination with a newly developed method f or estimation of repertoire diversity in complex mixtures of antibodies. Ou r results demonstrate that 60% of BMT patients have severely reduced divers ity in the IgM repertoire during and after the first year post-BMT, compare d with healthy controls. In contrast, the majority of patients have a polyc lonal IgG repertoire, similar to that of healthy controls. Serum IgM repert oires remain oligoclonal even though the serum concentration of total IgM i s within normal range around 6 months post-BMT. During the first years afte r transplantation IgM as well as IgG repertoires are less diverse in patien ts receiving a BM graft from a sibling donor compared with those receiving a graft from an HLA-matched unrelated donor. Patients in the latter group s how a higher incidence of infections and minor antigen mismatches which may promote the development of a diverse immunoglobulin repertoire post-BMT.