B cell reconstitution after human bone marrow transplantation: recapitulation of ontogeny?

Patients undergoing BMT have a long-lasting defect of B cell-mediated immunity, especially if chronic GVHD ensues. It has been postulated that the post-transplant B cell abnormalities can be explained by the recapitulation of B cell ontogeny. To test this hypothesis, we studied the quantitative and phenotypic reconstitution of circulating B cells in 24 transplant recipients and compared it with normal ontogeny. The results confirm that a second round of ontogeny occurs in transplant recipients without chronic GVHD. This was evidenced by the pattern of quantitative B cell reconstitution (low-->high-->normal B cell counts), large B cell size and a high proportion of B cells overexpressing CD38, membrane IgM (mIgM) and membrane IgD (mIgD). The recapitulation of ontogeny was blunted in most patients with chronic GVHD, as evidenced by the absence of the overshoot of total B cells and by the relative lack of CD38high, mIgMhigh and mIgDhigh B cells. We conclude the post-transplant B cell development in patients without chronic GVHD parallels ontogeny. The limited ability of patients with chronic GVHD to re-enact B cell ontogeny may contribute to their longer-lasting and more severe humoral immunodeficiency.