title: Cutting edge: transplant tolerance induced by anti-CD45RB requires B lymphocytes.
abstract: Selective interference with the CD45RB isoform by mAb (anti-CD45RB) reliably induces donor-specific tolerance. Although previous studies suggest participation of regulatory T cells, a mechanistic understanding of anti-CD45RB-induced tolerance is lacking. We report herein the unexpected finding that tolerance induced by this agent is not established in B cell-deficient mice but can be recovered by preemptive B lymphocyte transfer to B cell-deficient hosts. Using B cells from genetically modified donors to reconstitute B cell-deficient recipients, we evaluate the role of B lymphocyte-expressed CD45RB, T cell costimulatory molecules, and the production of Abs in this novel tolerance mechanism. Our data document an Ab-induced tolerance regimen that is uniquely B lymphocyte-dependent and suggest mechanistic contributions to tolerance development from the B cell compartment through interactions with T cells.
authors.affiliation: Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA. dengs@mail.med.upenn.edu
authors.forename: Shaoping
authors.initials: S
authors.lastname: Deng
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Moore
authors.forename: Xiaolun
authors.initials: X
authors.lastname: Huang
authors.forename: Moh-Moh
authors.initials: MM
authors.lastname: Lian
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mohiuddin
authors.forename: Ergun
authors.initials: E
authors.lastname: Velededeoglu
authors.forename: Major K
authors.initials: MK
authors.lastname: Lee
authors.forename: Samsher
authors.initials: S
authors.lastname: Sonawane
authors.forename: James
authors.initials: J
authors.lastname: Kim
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Haiying
authors.initials: H
authors.lastname: Chen
authors.forename: Steven A
authors.initials: SA
authors.lastname: Corfe
authors.forename: Christopher
authors.initials: C
authors.lastname: Paige
authors.forename: Mark
authors.initials: M
authors.lastname: Shlomchik
authors.forename: Andrew
authors.initials: A
authors.lastname: Caton
authors.forename: James F
authors.initials: JF
authors.lastname: Markmann
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000637:transplantation; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D016027:Heart Transplantation / Q000276:immunology*; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D023001:Transplantation Tolerance / Q000235:genetics / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D017493:Leukocyte Common Antigens