Research Papers: Immunology:
Collaboration between tumorspecific CD4+ T cells and B cells in anticancer immunity
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Thomas V. Guy1,2, Alexandra M. Terry1,2, Holly A. Bolton1,2, David G. Hancock1,2, Erhua Zhu1,2, Robert Brink3, Helen M. McGuire1,2, Elena Shklovskaya1,2,* and Barbara Fazekas de St Groth1,2,*
1 T Cell Biology Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, Sydney, NSW, Australia
2 Discipline of Dermatology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
3 B Cell Laboratory, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
* These authors have contributed equally to this work
Correspondence to:
Elena Shklovskaya, email:
Barbara Fazekas de St Groth, email:
Keywords: melanoma, antibody, B cell, CD4 T cell, Immunology and Microbiology Section, Immune response, Immunity
Received: March 07, 2016 Accepted: April 08, 2016 Published: April 18, 2016
Abstract
The role of B cells and antibodies in anti-tumor immunity is controversial, with both positive and negative effects reported in animal models and clinical studies. We developed a murine B16.F10 melanoma model to study the effects of collaboration between tumor-specific CD4+ T cells and B cells on tumor control. By incorporating T cell receptor transgenic T cells and B cell receptor isotype switching B cells, we were able to track the responses of tumor-reactive T and B cells and the development of anti-tumor antibodies in vivo. In the presence of tumor-specific B cells, the number of tumor-reactive CD4+ T cells was reduced in lymphoid tissues and the tumor itself, and this correlated with poor tumor control. B cells had little effect on the Th1 bias of the CD4+ T cell response, and the number of induced FoxP3+ regulatory cells (iTregs) generated from within the original naive CD4+ T cell inoculum was unrelated to the degree of B cell expansion. In response to CD4+ T cell help, B cells produced a range of isotype-switched anti-tumor antibodies, principally IgG1, IgG2a/c and IgG2b. In the absence of CD4+ T cells, B cells responded to agonistic anti-CD40 administration by switching to production of IgG2a/c and, to a lesser extent, IgG1, IgG3, IgA and IgE, which reduced the number of lung metastases after i.v. tumor inoculation but had no effect on the growth of subcutaneous tumors.