The absence of professional antigen presenting cells (APC) in the brain contributes to immune ignorance to antigen (Ag), including tumor Ag, localized exclusively within the brain parenchyma. Infiltration of APC or systemic priming of adaptive immune responses can overcome immune ignorance. However, the role of B cells in overcoming immune ignorance against brain tumor Ag has not yet been elucidated. In this study, we demonstrate that B cells are necessary to overcome immune ignorance in the brain and mount effective, tumor specific immune responses in vivo. Intratumoral expression of Fms-like tyrosine kinase 3 ligand (Flt3 ligand) and Herpes Simplex Virus 1 Thymidine Kinase (HSV1-TK) induced long term survival in C57BL/6 mice bearing syngeneic GL26 intracranial brain tumors. Clonal expansion of Trp2(180-188) tumor Ag specific T cells was observed in wild type mice, however, clonal expansion of tumor Ag specific T cells and long term survival were both abolished in B cell deficient mice. B cells increased in draining lymph nodes after treatment with Flt3 ligand and HSV1-TK and were capable of inducing T cell proliferation when loaded with Trp2(180-188) tumor antigen. Together, our data demonstrate a role for B cells as APC in surmounting immune ignorance by propagating afferent immune responses against brain tumor Ag.
Funded by NINDS 1RO1 NS 42893.01, U54 NS045309-01, 1R21 NS047298-01; and Bram & Elaine Goldsmith Chair in Gene Therapeutics to P.R.L.; NINDS 1R01 NS44556.01, and NIDDK 1 RO3 TW006273-01 to MGC; The Linda Tallen & David Paul Kane Foundation and the Board of Governors at CSMS.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA