Reconstitution of human immunoglobulin VH repertoire after bone marrow transplantation mimics B-cell ontogeny

Reconstitution of the human Ig repertoire after allogeneic and autologous bone marrow transplantation (BMT) was followed by analysis of the expression of the six VH families using in situ hybridization on BM cells at 30, 60, and 90 days postgraft. Our results indicate that during the early post-transplantation period, the expressed repertoire of VH is dramatically affected: VH3, the major expressed family in adult B cells, is decreased two- to threefold and is compensated by transient overexpression of the other families, especially VH4, VH5, and VH6. Similar results were observed in allogeneic and autologous grafted patients. Kinetics of reconstitution mimics normal repertoire development described in ontogeny, although normalization, as compared with the adult pattern, may take as long as 1 year.