Increased rejection of primary tumors in mice lacking B cells: inhibition of anti-tumor CTL and TH1 cytokine responses by B cells.
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 T(H)1 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 T(H)1 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-gamma 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 T(H)1 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.
Shah
Sangeeta
S
Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, FL 33136, USA.
Divekar
Anagha A
AA
Hilchey
Shannon P
SP
Cho
Hyun-Mi
HM
Newman
Corliss L
CL
Shin
Seung-Uon
SU
Nechustan
Hovav
H
Challita-Eid
Pia M
PM
Segal
Benjamin M
BM
Yi
Kyung Hee
KH
Rosenblatt
Joseph D
JD
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D008212:Lymphocyte Depletion; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D016207:Cytokines