title: B-cell depletion improves islet allograft survival with anti-CD45RB.
abstract: A short course of anti-CD45RB leads to long-term islet allograft survival and donor-specific tolerance in approximately half of immunocompetent mice. We have previously demonstrated that anti-CD45RB antibody-mediated tolerance requires B-cells for cardiac allograft survival. We therefore asked whether B-cells were also required for anti-CD45RB antibody-mediated survival of islets. Unexpectedly, we found that nearly 100% of islet allografts survive long term in B-cell-deficient mice. Similarly, B-cell depletion by anti-CD22/cal augmented anti-CD45RB-mediated tolerance when administered pretransplant, although it had no effect on tolerance induction when administered posttransplant. Our results demonstrate that the role of B-cells in promoting tolerance with anti-CD45RB is graft specific, promoting tolerance in cardiac grafts but resisting tolerance in islet transplantation. These findings may help elucidate the varied action of B-cells in promoting tolerance versus rejection.
authors.affiliation: Transplantation Unit, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Kang Mi
authors.initials: KM
authors.lastname: Lee
authors.forename: Heidi
authors.initials: H
authors.lastname: Yeh
authors.forename: Gaoping
authors.initials: G
authors.lastname: Zhao
authors.forename: Lingling
authors.initials: L
authors.lastname: Wei
authors.forename: Matthew
authors.initials: M
authors.lastname: O'Connor
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Stott
authors.forename: Julie
authors.initials: J
authors.lastname: Soohoo
authors.forename: Kyri
authors.initials: K
authors.lastname: Dunussi
authors.forename: Paolo
authors.initials: P
authors.lastname: Fiorina
authors.forename: Shaoping
authors.initials: S
authors.lastname: Deng
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
authors.forename: James I
authors.initials: JI
authors.lastname: Kim
mesh_terms: D064591:Allografts; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D004195:Disease Models, Animal; D006085:Graft Survival / Q000276:immunology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000379:methods*; D017493:Leukocyte Common Antigens / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D017493:Leukocyte Common Antigens