The effect of chronic graft-versus-host disease on B cell development.
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 x B10.D2)F1 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-->F1 splenic B cells does not restore the colony-forming 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.
Schreiber
K L
KL
Immunology Program, University of Texas Southwestern Medical Center, Dallas 75235-9048.
Forman
J
J
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001854:Bone Marrow Cells; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000473:pathology / Q000503:physiopathology*; D016219:Immunotherapy, Adoptive; D008070:Lipopolysaccharides / Q000494:pharmacology; D008198:Lymph Nodes / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D013154:Spleen / Q000473:pathology
D008070:Lipopolysaccharides; D015778:Minor Histocompatibility Antigens