Coexpression of B7-1 and antigen blocks tolerance induction to antigen presented by resting B cells.
To investigate a role for B cells as tolerogenic APCs in peripheral lymphoid organs, we have developed a system in which B cells from mice transgenic for the membrane-bound form of human mu-chain are transferred into nontransgenic recipients. Mice injected with B cells expressing human mu-chain became profoundly tolerant to human mu-chain, as shown by greatly reduced Ab responses following challenge with human mu-chain in adjuvant. Adoptive transfer experiments showed that the recipient's Th cell response to human mu-chain was impaired. When the human mu transgenic spleen cells were activated with LPS before transfer, they no longer induced tolerance. Spleen cells from double-transgenic mice expressing both human mu-chain and the costimulatory molecule B7-1 (CD80) also failed to induce tolerance to human mu-chain. However, neither human mu transgenic LPS blasts nor double-transgenic B cells induced an Ab response or primed for a secondary Ab response to Ag in adjuvant. Therefore, we find that expression of B7-1 together with Ag can interfere with tolerance induction without inducing Ab formation or priming for a secondary Ab response.
Yuschenkoff
V N
VN
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester 01655, USA.
Sethna
M P
MP
Freeman
G J
GJ
Parker
D C
DC
D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000637:transplantation; D001402:B-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000276:immunology; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007148:Immunoglobulin mu-Chains / Q000008:administration & dosage / Q000276:immunology; D007275:Injections, Intravenous; D007399:Interphase / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017634:Self Tolerance
D018122:B7-1 Antigen; D007148:Immunoglobulin mu-Chains; D008070:Lipopolysaccharides