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Resting B Cells Suppress Tumor Immunity via an MHC Class-II Dependent Mechanism

Watt, Victoria*; Ronchese, Franca*; Ritchie, David* †

doi: 10.1097/CJI.0b013e31802bd9c8
Basic Studies
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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-β 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.

*Malaghan Institute of Medical Research, Wellington, New Zealand

Peter MacCallum Cancer Centre, East Melbourne, Australia

Financial Disclosure: The authors have declared there are no financial conflicts of interest related to this work.

Reprints: David Ritchie, Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, Locked Bag 1, A'Beckett St, East Melbourne 8006, Australia (e-mail: david.ritchie@petermac.org).

Received for publication September 11, 2006; accepted September 25, 2006

Supported by the University of Otago Post-graduate Scholarships and Research Committee PhD Publishing Award.

© 2007 Lippincott Williams & Wilkins, Inc.