Calcineurin inhibitors block B-1 cell differentiation: the relevance to immunosuppressive treatment in ABO-incompatible transplantation.
Naturally occurring antibodies (Abs) against human blood group A/B-carbohydrate determinants are a major barrier to ABO-incompatible organ transplantation. We previously described that B cells recognizing the blood group A antigens (Ag) belong to a CD5+ B-1a cell subset that exists in blood group O human peripheral blood as well as in mice Recent evidence suggests that B-1a cells are selected by a T-independent type 2 (TI-2) Ag with repetitive arrays of epitopes which can promote BCR cross-linking. In support of the induced-differentiation model, CD5 can be induced on spleen B-2 cells in vitro after stimulation via surface IgM receptors, an induction that is blocked by cyclosporine (CsA). We examined whether mouse peritoneal cavity CD5+ B-1a cells could be reduced by CsA/tacrolimus. For 2 weeks, daily intraperitoneal (i.p.) injection of various doses of CsA/tacrolimus decreased the percentage of PerC CD5+ B-1a cells and increased B-2 cells in a dose-dependent fashion. However, this treatment had no impact on anti-A Abs, suggesting that Ab-producing cells may be resistant to calcineurin inhibitors. We speculate that specific elimination of the anti-A Ab-producing cells with subsequent CsA/tacrolimus therapy might induce lasting inhibition of anti-A Ab production in ABO-incompatible organ transplantation.
Zhou
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W
Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi, Hiroshima, Japan.
Ohdan
H
H
Asahara
T
T
D000017:ABO Blood-Group System; D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D001787:Blood Group Incompatibility; D065095:Calcineurin Inhibitors; D002454:Cell Differentiation / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D016559:Tacrolimus / Q000494:pharmacology
D000017:ABO Blood-Group System; D000943:Antigens, Differentiation; D065095:Calcineurin Inhibitors; D016572:Cyclosporine; D016559:Tacrolimus