title: Anti-CD45RB/anti-TIM-1-induced tolerance requires regulatory B cells.
abstract: The role of B cells in transplant tolerance remains unclear. Although B-cell depletion often prolongs graft survival, sometimes it results in more rapid rejection, suggesting that B cells may have regulatory activity. We previously demonstrated that tolerance induction by anti-CD45RB antibody requires recipient B cells. Here, we show that anti-CD45RB in combination with anti-TIM-1 antibody has a synergistic effect, inducing tolerance in all recipients in a mouse islet allograft model. This effect depends on the presence of recipient B cells, requires B-cell IL-10 activity, and is antigen-specific. These data suggest the existence of a regulatory B-cell population that promotes tolerance via an IL-10-dependent pathway.
authors.affiliation: Division of Transplantation, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Lee
authors.forename: J I
authors.initials: JI
authors.lastname: Kim
authors.forename: R
authors.initials: R
authors.lastname: Stott
authors.forename: J
authors.initials: J
authors.lastname: Soohoo
authors.forename: M R
authors.initials: MR
authors.lastname: O'Connor
authors.forename: H
authors.initials: H
authors.lastname: Yeh
authors.forename: G
authors.initials: G
authors.lastname: Zhao
authors.forename: P
authors.initials: P
authors.lastname: Eliades
authors.forename: C
authors.initials: C
authors.lastname: Fox
authors.forename: N
authors.initials: N
authors.lastname: Cheng
authors.forename: S
authors.initials: S
authors.lastname: Deng
authors.forename: J F
authors.initials: JF
authors.lastname: Markmann
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D000072596:Hepatitis A Virus Cellular Receptor 1; D007108:Immune Tolerance; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: C442240:Havcr1 protein, mouse; D000072596:Hepatitis A Virus Cellular Receptor 1; D008565:Membrane Proteins; D017493:Leukocyte Common Antigens