Calcineurin inhibitors block B-1 cell differentiation: the relevance to immunosuppressive treatment in ABO-incompatible transplantation.
Transplant Proc
; 37(4): 1808-11, 2005 May.
Article
em En
| MEDLINE
| ID: mdl-15919474
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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Base de dados:
MEDLINE
Assunto principal:
Incompatibilidade de Grupos Sanguíneos
/
Sistema ABO de Grupos Sanguíneos
/
Linfócitos B
/
Ciclosporina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Transplant Proc
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Japão