title: Cutting Edge: IL-10 Is Essential for the Generation of Germinal Center B Cell Responses and Anti-Plasmodium Humoral Immunity.
abstract: IL-10 is a pleiotropic cytokine expressed during malaria, a disease characterized by short-lived, parasite-specific Ab responses. The role of IL-10 in regulating B cell responses during malaria is not known. In this study we report that IL-10 is essential for anti-Plasmodium humoral immunity. We identify that germinal center (GC) B cell reactions, isotype-switched Ab responses, parasite control, and host survival require B cell-intrinsic IL-10 signaling. IL-10 also indirectly supports humoral immunity by suppressing excessive IFN-γ, which induces T-bet expression in B cells. Genetic ablation of either IFN-γ signaling or T-bet expression in B cells substantially enhanced GC B cell responses and anti-Plasmodium Ab production. Together, our data show that B cell-intrinsic IL-10 enhances whereas B cell-intrinsic IFN-γ and T-bet suppress GC B cell responses and anti-Plasmodium humoral immunity. These data identify critical immunoregulatory circuits in B cells that may be targeted to promote long-lived humoral immunity and resistance to malaria.
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors.forename: Jenna J
authors.initials: JJ
authors.lastname: Guthmiller
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Graham
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.|Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53213; and.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Zander
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors.forename: Rosemary L
authors.initials: RL
authors.lastname: Pope
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; noah-butler@ouhsc.edu.|Graduate Program in Biomedical Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
authors.forename: Noah S
authors.identifier: 0000-0002-1429-0796
authors.initials: NS
authors.lastname: Butler
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010967:Plasmodium yoelii
chemical_list: D000913:Antibodies, Protozoan; C556062:IL10 protein, mouse; D016753:Interleukin-10