B-cell-autonomous somatic mutation deficit following bone marrow transplant

Hematopoietic stem cell transplantation is characterized by a prolonged per iod of humoral immunodeficiency, We have previously shown that the deficien cies are probably not due to the failure to utilize the appropriate V regio ns in the preimmune repertoire. However, a striking observation, which corr elated with the absence of immunoglobulin IgD(-) cells and was consistent w ith a defect in antigen-driven responses, was that rearrangements in bone m arrow transplant (BMT) recipients exhibited much less somatic mutation than did rearrangements obtained from healthy subjects. In this paper, we prese nt evidence suggesting that naive B cells obtained from BMT recipients lack the capacity to accumulate somatic mutations in a T-cell-dependent manner compared with healthy subjects, This appears to be a B-cell-autonomous defi cit because T cells from some patients, which were not able to support the accumulation of mutations in autologous naive B cells, were able to support accumulation of mutations in heterologous healthy-subject naive B cells. ( C) 2000 by The American Society of Hematology.