Collaboration between tumor-specific CD4+ T cells and B cells in anti-cancer immunity.
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.
T Cell Biology Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, Sydney, NSW, Australia.|Discipline of Dermatology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Thomas V
TV
Guy
T Cell Biology Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, Sydney, NSW, Australia.|Discipline of Dermatology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Alexandra M
AM
Terry
T Cell Biology Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, Sydney, NSW, Australia.|Discipline of Dermatology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Holly A
HA
Bolton
T Cell Biology Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, Sydney, NSW, Australia.|Discipline of Dermatology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
David G
DG
Hancock
T Cell Biology Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, Sydney, NSW, Australia.|Discipline of Dermatology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Erhua
E
Zhu
B Cell Laboratory, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Robert
R
Brink
T Cell Biology Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, Sydney, NSW, Australia.|Discipline of Dermatology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Helen M
HM
McGuire
T Cell Biology Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, Sydney, NSW, Australia.|Discipline of Dermatology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Elena
E
Shklovskaya
T Cell Biology Laboratory, Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, Sydney, NSW, Australia.|Discipline of Dermatology, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.
Barbara
B
Fazekas de St. Groth
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D047368:Tumor Burden / Q000235:genetics / Q000276:immunology
D016207:Cytokines
B cell; CD4 T cell; Immune response; Immunity; Immunology and Microbiology Section; antibody; melanoma