Cutting edge: transplant tolerance induced by anti-CD45RB requires B lymphocytes.
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.
Deng
Shaoping
S
Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA. dengs@mail.med.upenn.edu
Moore
Daniel J
DJ
Huang
Xiaolun
X
Lian
Moh-Moh
MM
Mohiuddin
Muhammad
M
Velededeoglu
Ergun
E
Lee
Major K
MK
Sonawane
Samsher
S
Kim
James
J
Wang
Jing
J
Chen
Haiying
H
Corfe
Steven A
SA
Paige
Christopher
C
Shlomchik
Mark
M
Caton
Andrew
A
Markmann
James F
JF
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*
D000911:Antibodies, Monoclonal; D017493:Leukocyte Common Antigens