B cells are required for optimal CD4+ and CD8+ T cell tumor immunity: therapeutic B cell depletion enhances B16 melanoma growth in mice.
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.
DiLillo
David J
DJ
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Yanaba
Koichi
K
Tedder
Thomas F
TF
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D008213:Lymphocyte Activation / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic