title: B cells promote tumor immunity against B16F10 melanoma.
abstract: B cells are known to be critical mediators of tumor immunity; however, the mechanisms through which they exert this function remain unclear. B-cell linker protein (BLNK) is an essential component of the B-cell antigen receptor signaling machinery and is required for B-cell development, as evidenced by BLNK-deficient (BLNK(-/-)) mice, in which the development and function of B cells are severely impaired. Herein, we evaluated the role of B cells in the development of tumor immunity against B16F10 melanoma using BLNK(-/-) mice. B16F10 melanoma grew more aggressively in BLNK(-/-) mice, resulting in a twofold increase in tumor volume compared with wild-type mice. As predicted, tumor-infiltrating B-cell numbers were decreased in BLNK(-/-) mice. Paradoxically, tumor-infiltrating T-cell numbers were decreased in BLNK(-/-) mice, although inguinal lymph node T-cell numbers were increased. Adoptive transfer of B cells from wild-type mice into BLNK(-/-) mice attenuated B16F10 melanoma growth, with increasing numbers of B and T cells infiltrating into tumors. In addition, percentages of interferon-γ- and tumor necrosis factor-α-producing tumor-infiltrating T cells were restored. Taken together, our study supports the concept that B cells enhance tumor immunity against B16F10 melanoma by promoting T-cell infiltration into tumors and cytokine production within the tumor microenvironment.
authors.affiliation: Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Hamaguchi
authors.affiliation: Department of Dermatology, University of Fukui, Fukui, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Takehara
authors.affiliation: Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan. Electronic address: t-matsushita@med.kanazawa-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsushita
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology*; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein