Antitumor Immunity and B Cells

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The innate and adaptive arms of the immune system have the capacity to kill tumors. This cytolytic function is fulfilled by the innate immune system through NK cells and by the adaptive immune system through CD8 cytotoxic effector T cells (CTL). Initiation of anti-tumor immunity requires the participation of macrophages, dendritic cells and NK cells, all members of the innate immune system. The induction adaptive immunity and the generation of tumor specific CD8 T cell effector killers (CTL) generally is dependent upon CD4 T cell help (Melero et al., 1997, 1998b). Relative to effective cell-mediated anti-tumor responses evidence suggesting that B cells play an important role in curative antitumor immunity is sparse and there is some evidence that B cells may contribute to tumor progression.

The notion that B cells might interfere with the induction of T cell mediated anti-tumor immunity was first suggested in experiments in which B cell development was blocked in neonatal mice that were subsequently inoculated with tumor cells. Compared with untreated littermates, tumor progression in these mice was markedly suppressed. More recently, Qin et al. demonstrated that it was possible to successfully vaccinate and protect BALB/c |MT B cell deficient mice against a variety of tumors (Qin et al., 1998). These studies strongly suggest that interplay between B cells and T cells suppress the development of anti-tumor immunity in |MT mice. For example, these transgenic B cell deficient mice have the capacity to develop anti-tumor immunity following vaccination with irradiated tumor cells whereas syngeneic wild type mice do not. Adoptive transfer of B cells into naïve |MT mice renders them refractive to vaccination and the mice succumb to the tumor (Qin et al., 1998). However, the mechanisms through which B cells mediate suppression of anti-tumor immunity are poorly understood. It has been suggested that B cells may exert their suppressive effect on the induction of anti-tumor immunity by virtue of their capacity to capture low levels of tumor antigens through their high affinity antigen receptors and thus sequester antigen from dendritic cells that prime T cells (Qin et al., 1998).

In humans, the prognosis in certain neoplastic diseases such as colorectal and ovarian cancer bears an inverse relationship between production of anti-oncogene antibody levels and disease progression (Houbiers et al., 1995; Morrin et al., 1994). If B cell-induced suppression of anti-tumor immunity occurs in humans as it has been observed in mice, novel treatment approaches based upon B cell depletion might find clinical applicability. Neuroblastoma, the most common non-cranial childhood cancer is one example that might benefit. Children with non-remitting neuroblastoma receive myeloablative whole body irradiation and chemotherapy followed by autologous bone marrow rescue. These procedures coupled with au-tologous T cell rescue might allow for successful patient vaccination against their tumors. For this reason we decided to study the phenomenon of B cell induced suppression of anti-tumor immune responses in mice. To pursue this study we followed the development of Lewis lung carcinoma (LLC) in C57BL/6 wild type, Rag-deficient, and |MT B cell deficient mice. Mice were vaccinated and/or inoculated

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