title: Regulatory B cells preferentially accumulate in tumor-draining lymph nodes and promote tumor growth.
abstract: Our previous studies found that B16-F10 melanoma growth in the rear footpad of immunocompetent mice induces marked B cell accumulation within tumor-draining popliteal lymph nodes (TDLN). This B cell accumulation drives TDLN remodeling that precedes and promotes metastasis, indicating a tumor-promoting role for TDLN B cells. Here we show that phenotypic characterization of lymphocytes in mice bearing B16-F10 melanomas identifies preferential accumulation of T2-MZP B cells in the TDLN. Comparison of non-draining LNs and spleens of tumor-bearing mice with LNs and spleens from naïve mice determined that this pattern of B cell accumulation was restricted to the TDLN. B cell-deficient and immunocompetent mice reconstituted with T2-MZP B cells but not with other B cell subsets displayed accelerated tumor growth, demonstrating that T2-MZP B cells possess regulatory activity in tumor-bearing mice. Unlike splenic regulatory B cells, however, these TDLN B cells did not exhibit increased IL-10 production, nor did they promote Treg generation in the TDLN. These findings demonstrate that tumors initially signal via the lymphatic drainage to stimulate the preferential accumulation of T2-MZP regulatory B cells. This local response may be an early and critical step in generating an immunosuppressive environment to permit tumor growth and metastasis.
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Sheila N
authors.initials: SN
authors.lastname: Ganti
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Tina C
authors.initials: TC
authors.lastname: Albershardt
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Iritani
authors.affiliation: 1] Department of Comparative Medicine, University of Washington, Seattle, WA, USA [2] Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Alanna
authors.initials: A
authors.lastname: Ruddell
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D049109:Cell Proliferation; D005260:Female; D008198:Lymph Nodes / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology