The absence of B lymphocytes reduces the number and function of T-regulatory cells and enhances the anti-tumor response in a murine tumor model.
Increasing evidence suggests that B lymphocytes play a central role in inhibiting the immune response against certain tumors, but the underlying mechanisms by which B cells facilitate tumor growth are still poorly understood. In this study, we investigated how the presence or absence of B cells affects expansion and function of T-regulatory cells ('T-regs') in a murine breast tumor model (EMT-6). We compared tumor growth, and the number and function of T-reg cells in wild-type immune-competent mice (ICM) and B-cell-deficient mice (BCDM). Mice were either tumor-naive or implanted with EMT-6 mammary adenocarcinoma cells. Tumor growth was markedly inhibited in BCDM, compared to wild-type mice (ICM). Increased T-reg expansion as defined by CD4+/CD25+/FOXP3+ cells was evident following EMT-6 inoculation in ICM in comparison with non-tumor-bearing mice or compared to BCDM in which tumor had been implanted. The percentage and absolute number of T-regs in the spleen, tumor draining lymph nodes, and tumor bed were significantly reduced in BCDM compared to ICM. T-reg function, measured by suppression and proliferation assays, was also reduced in tumor inoculated BCDM compared to ICM. Our studies indicate that absence of B cells may play a role in augmenting the T-cell anti-tumor response, in part due to effects on T-regulatory cell expansion and function.
Haematology Unit, Bnai Zion Medical Center, Haifa, Israel.
Tamar
T
Tadmor
Yu
Y
Zhang
Hyun-Mi
HM
Cho
Eckhard R
ER
Podack
Joseph D
JD
Rosenblatt
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000032:analysis; D016130:Immunophenotyping; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit
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