Chronic graft-versus-host disease often results in a combined deficiency of humoral and cell-mediated immunity. Clinical and experimental studies have suggested that the decrease in B cell responsiveness is due to a failure of B cell production in the bone marrow, intrinsic B cell defects, excessive suppressor T cell activity, and deficient T helper activity. In the present study, we analyze the basis of B cell immunodeficiency in C.B-20→(C.B-20×B10.D2)Fi animals afflicted with chronic GVHD. The initial decline in B cell production in the BM accounts for the early reduction in the number of B cells in the spleen and BM. Later, as B cells appear in near-normal numbers in the BM, the spleen and lymph node are repopulated by the newly derived B cells. Associated with the appearance of B cells in the BM and spleen is the ability to respond to lipopolysaccharide. In contrast, both B cell populations are severely diminished in their ability to proliferate in response to agar-derived mitogens to form colonies (CFU-B). The reduction in the CFU-B response is most likely a consequence of an inherent B cell defect, since purification of C.B-20→Fi splenic B cells does not restore the colonyforming potential. Unlike BM and splenic B cells, LN B cells are unable to respond to either mitogen. Taken together, these results imply that a population of B cells derived from a distinct lineage and/or B cell maturation is defective in mice undergoing GVHD.
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