title: Macrophage regulation of B cell proliferation.
abstract: Unlike organized lymphoid tissue, the tumor microenvironment (TME) often includes a high proportion of immunosuppressive macrophages. We model the TME by culturing peritoneal cavity (PerC) cells that naturally have a high macrophage to lymphocyte ratio. Prior studies revealed that, following TCR ligation, PerC T cell proliferation is suppressed due to IFNγ-triggered inducible nitric oxide synthase expression. In this study we assessed the ability of PerC B cells to respond to surrogate activating signals in the presence of high numbers of macrophages. Surface IgM (BCR) ligation led to cyclooxygenase-mediated, and TLR-4 ligation to IL10-mediated, suppression of PerC B cell proliferation. In contrast, PerC B cells had a robust response to CD40 ligation, which could overcome the suppression generated by the BCR or TLR-4 response. However, the CD40 response was suppressed by concurrent TCR ligation. These results reveal the challenges of promoting B and T cell responses in macrophage-rich conditions that model the TME.
authors.affiliation: Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Goldman
authors.affiliation: Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
authors.forename: Kornelija
authors.initials: K
authors.lastname: Valiuskyte
authors.affiliation: Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Londregan
authors.affiliation: Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Swider
authors.affiliation: Department of Biology, Rider University, Lawrenceville, NJ 08648, USA.
authors.forename: John
authors.initials: J
authors.lastname: Somerville
authors.affiliation: Department of Biology, Rider University, Lawrenceville, NJ 08648, USA. Electronic address: riggs@rider.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Riggs
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D010529:Peritoneal Cavity / Q000473:pathology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D019013:CD40 Antigens; D011948:Receptors, Antigen, T-Cell; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II
keywords: B cell; CD40; Macrophage; Tumor microenvironment