title: Regulatory B Cell-Dependent Islet Transplant Tolerance Is Also Natural Killer Cell Dependent.
abstract: Immunologic tolerance to solid organ and islet cell grafts has been achieved in various rodent models by using antibodies directed at CD45RB and Tim-1. We have shown that this form of tolerance depends on regulatory B cells (Bregs). To elucidate further the mechanism by which Bregs induce tolerance, we investigated the requirement of natural killer (NK) and NKT cells in this model. To do so, hyperglycemic B6, μMT, Beige, or CD1d-/-mice received BALB/c islet grafts and treatment with the tolerance-inducing regimen consisting of anti-CD45RB and anti-TIM1. B6 mice depleted of both NK and NKT cells by anti-NK1.1 antibody and mice deficient in NK activity (Beige) did not develop tolerance after dual-antibody treatment. In contrast, transplant tolerance induction was successful in CD1d-/-recipients (deficient in NKT cells), indicating that NK, but not NKT, cells are essential in B cell-dependent tolerance. In addition, reconstitution of Beige host with NK cells restored the ability to induce transplant tolerance with dual-antibody treatment. Transfer of tolerance by B cells from tolerant mice was also dependent on host Nk1.1+cells. In conclusion, these results show that regulatory function of B cells is dependent on NK cells in this model of transplantation tolerance.
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: C
authors.initials: C
authors.lastname: Schuetz
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: K M
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: R
authors.initials: R
authors.lastname: Scott
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: L
authors.initials: L
authors.lastname: Kojima
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: L
authors.initials: L
authors.lastname: Washburn
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: W-H
authors.initials: WH
authors.lastname: Liu
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: H
authors.initials: H
authors.lastname: Tector
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: J
authors.initials: J
authors.lastname: Lei
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: H
authors.initials: H
authors.lastname: Yeh
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: J I
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Boston, MA.
authors.forename: J F
authors.initials: JF
authors.lastname: Markmann
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D005260:Female; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal
keywords: B cell biology; basic (laboratory) research/science; immunobiology; islet transplantation; natural killer (NK) cells/NK receptors; tolerance