B Cells Are Required for Optimal CD4+ and CD8+ T Cell Tumor Immunity: Therapeutic B Cell Depletion Enhances B16 Melanoma Growth in Mice

• Published in: The Journal of immunology (1950) Vol. 184; no. 7; pp. 4006 - 4016
• Main Authors: DiLillo, David J, Yanaba, Koichi, Tedder, Thomas F
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.04.2010
• Subjects: Adoptive Transfer; Animals; B-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Separation; Flow Cytometry; Fluorescent Antibody Technique; Lymphocyte Activation - immunology; Melanoma, Experimental - immunology; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; Mice, Transgenic
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0903009

B lymphocytes can both positively and negatively regulate cellular immune responses. Previous studies have demonstrated augmented T cell-mediated tumor immunity in genetically B cell-deficient mice, suggesting that therapeutic B cell depletion would enhance tumor immunity. To test this hypothesis and quantify B cell contributions to T cell-mediated anti-tumor immune responses, mature B cells were depleted from wild-type adult mice using CD20 mAb prior to syngeneic B16 melanoma tumor transfers. Remarkably, s.c. tumor volume and lung metastasis were increased 2-fold in B cell-depleted mice. Effector-memory and IFN-gamma-or TNF-alpha-secreting CD4(+) and CD8(+) T cell induction was significantly impaired in B cell-depleted mice with tumors. Tumor Ag-specific CD8(+) T cell proliferation was also impaired in tumor-bearing mice that lacked B cells. Thus, B cells were required for optimal T cell activation and cellular immunity in this in vivo nonlymphoid tumor model. Although B cells may not have direct effector roles in tumor immunity, impaired T cell activation, and enhanced tumor growth in the absence of B cells argue against previous proposals to augment tumor immunity through B cell depletion. Rather, targeting tumor Ags to B cells in addition to dendritic cells is likely to optimize tumor-directed vaccines and immunotherapies.