Increased rejection of primary tumors in mice lacking B cells: Inhibition of anti-tumor CTL and TH1 cytokine responses by B cells

Sangeeta Shah, Anagha A. Divekar, Shannon P. Hilchey, Hyun Mi Cho, Corliss L. Newman, Seung Uon Shin, Hovav Nechustan, Pia M. Challita-Eid, Benjamin M. Segal, Kyung Hee Yi, Joseph D. Rosenblatt

Research output: Contribution to journalArticle

150 Scopus citations

Abstract

We investigated the role of B cells in tumor immunity by studying immune responses of mice genetically lacking B cells to primary tumors. IgM -/- B cell-deficient mice (BCDM) exhibited enhanced resistance to 3 histologically diverse syngeneic tumors as compared to the wild-type (WT) mice. EL4 thymoma and MC38 colon carcinoma grew progressively in WT mice, but regressed spontaneously in BCDM whereas growth of B16 melanoma was slowed significantly in BCDM as compared to the WT mice. BCDM exhibited increased T cell infiltration of tumors, higher TH1 cytokine response and, in the case of MC38, a higher anti-tumor CTL response. The increased tumor resistance of BCDM did not seem to result from intrinsic changes in their non-B immunocytes because adoptive transfer of WT splenic B cells to BCDM abrogated tumor rejection and resulted in diminished anti-tumor TH1 cytokine and CTL responses. Studies involving BCR-transgenic mice indicated that B cells may inhibit anti-tumor T cell responses by antigen-nonspecific mechanisms since neither tumor-specific antibodies nor cognate T:B interactions were necessary for inhibition of tumor immunity by B cells. IFN-γ secretion in splenocyte:-tumor co-cultures of tumor-challenged BCDM was inhibited by WT but not CD40-/- B cells indicating that B cells may inhibit anti-tumor TH1 cytokine responses in a CD40-dependent manner. Adoptive transfer of CD40-/- B cells into BCDM resulted in restored growth of MC38 suggesting additional factors other than CD40 are involved in dampening anti-tumor responses. The effects of B cells on anti-tumor response warrant further study.

Original languageEnglish (US)
Pages (from-to)574-586
Number of pages13
JournalInternational Journal of Cancer
Volume117
Issue number4
DOIs
StatePublished - Nov 20 2005

Keywords

  • Anti-tumor immunity
  • B cell-deficiency
  • B lymphocytes
  • Primary tumors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Shah, S., Divekar, A. A., Hilchey, S. P., Cho, H. M., Newman, C. L., Shin, S. U., Nechustan, H., Challita-Eid, P. M., Segal, B. M., Yi, K. H., & Rosenblatt, J. D. (2005). Increased rejection of primary tumors in mice lacking B cells: Inhibition of anti-tumor CTL and TH1 cytokine responses by B cells. International Journal of Cancer, 117(4), 574-586. https://doi.org/10.1002/ijc.21177