B Cells Inhibit Induction of T Cell-dependent Tumor Immunity

Cytotoxic T lymphocyte (CTL) mediated tumor immunity against major histocompatibility antigen (MHC) class I-positive but class II-negative tumors often requires help from CD4+ T cells. These CD4 cells are activated by MHC class II-positive cells that present tumor derived antigens. Considering that different antigen presenting cells, such as B cells, macrophages and dendritic cells compete for antigen and influence the outcome of an immune response, we analyzed tumor immunity in B cell-deficient mice. These mice appear normal with regard to T cell immunity and tolerance to some pure foreign antigens. We show here that the low immunogenicity of tumors is caused by B cells whose presence in the priming phase results in disabled CD4+ T cell help for CTL mediated tumor immunity. Instead, in the presence of B cells, a non-protective humoral immune response is induced. Our results may explain the enigmatic observation that tumor-reactive antibodies occur frequently in cancer patients.