Resting B cells suppress tumor immunity via an MHC class-II dependent mechanism.
Resting B cells have been variously shown to induce direct tolerance of antigen specific CD8+ T cells, induce T-cell anergy via transforming growth factor-beta production, down-regulate interleukin-12 production by dendritic cells (DC) and influence TH1/TH2 differentiation via the production of regulatory cytokines. Through these mechanisms, B cells can exert a regulatory function in in vivo models of T-cell immunity including, experimental autoimmune encephalitis and rheumatoid arthritis. Here, we show that the resting B cells inhibit the ability of DC vaccination to provide protection from tumor growth. Inhibition of DC induced immunity by B cells was independent of presentation of major histocompatibility molecule (MHC) class-I bound tumor antigen but dependent on B-cell expression of MHC class-II. Administration of B cells did not alter the ability of DC to migrate from the injection site or impair DC-T cell interactions within the draining lymph node. The inhibitory effect of B cells was lost when they were activated by CD40L and partially reversed by the depletion of CD4+/CD25+ regulatory T cells. Together our findings indicate that the resting B cells are capable of limiting CD8+ T-cell effector function induced by DC vaccination via a mechanism that is dependent on the expression of MHC class-II molecules.
Watt
Victoria
V
Malaghan Institute of Medical Research, Wellington, New Zealand.
Ronchese
Franca
F
Ritchie
David
D
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D023201:CD40 Ligand / Q000494:pharmacology; D002465:Cell Movement; D017635:Clonal Anergy; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology*; D016192:Resting Phase, Cell Cycle; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014611:Vaccination
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D053645:Interleukin-2 Receptor alpha Subunit; D023201:CD40 Ligand