Balin, Samuel J.

Abstract Although T cells and B cells can respond immunologically to some tumors, whether and how they collaborate to control tumor growth is incompletely understood. To address this question we introduced a foreign antigen (HIV envelope), as a model for a tumor antigen, linked to C3d (AgC3d) in a tumor cell line and tested the fate of that line in isogeneic mice. AgC3d-positive tumors invoked antigen-specific antibodies and T cell-mediated IFN gamma secretion. Tumors expressing AgC3d grew more slowly than non-transfected cells and mice with tumors expressing AgC3d survived longer than mice with tumor alone. Slower growth of tumors was due to immunity directed against the viral antigen since AgC3d-positive tumors grew as fast as AgC3d-negative tumors in immune-deficient RAG-2 gammac-deficient hosts. Immunity and control of tumor growth required C3d since tumors expressing the antigen without C3d grew slower than tumors expressing AgC3d. Anti-tumor immunity depended on CR2 since tumors implanted in mice treated with CR2-Ig grew more rapidly than tumors grown in the absence of CR2-Ig. Control of tumors was not the direct result of C3d interaction with B cell CR2 as AgC3d-positive tumors grew slower and in some cases regressed in B cell deficient (JH-/-) mice than in wild type mice. Our findings suggest that C3d enables antigen specific responses by T cells and this response may be regulated by B cells.