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Transplant Proc. 2005 May;37(4):1808-11.

Calcineurin inhibitors block B-1 cell differentiation: the relevance to immunosuppressive treatment in ABO-incompatible transplantation.

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1
Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi, Hiroshima, Japan.

Abstract

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.

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