title: Splenic B cells from Hymenolepis diminuta-infected mice ameliorate colitis independent of T cells and via cooperation with macrophages.
abstract: Helminth parasites provoke multicellular immune responses in their hosts that can suppress concomitant disease. The gut lumen-dwelling tapeworm Hymenolepis diminuta, unlike other parasites assessed as helminth therapy, causes no host tissue damage while potently suppressing murine colitis. With the goal of harnessing the immunomodulatory capacity of infection with H. diminuta, we assessed the putative generation of anti-colitic regulatory B cells following H. diminuta infection. Splenic CD19(+) B cells isolated from mice infected 7 [HdBc(7(d))] and 14 d (but not 3 d) previously with H. diminuta and transferred to naive mice significantly reduced the severity of dinitrobenzene sulfonic acid (DNBS)-, oxazolone-, and dextran-sodium sulfate-induced colitis. Mechanistic studies with the DNBS model, revealed the anti-colitic HdBc(7(d)) was within the follicular B cell population and its phenotype was not dependent on IL-4 or IL-10. The HdBc(7(d)) were not characterized by increased expression of CD1d, CD5, CD23, or IL-10 production, but did spontaneously, and upon LPS plus anti-CD40 stimulation, produce more TGF-β than CD19(+) B cells from controls. DNBS-induced colitis in RAG1(-/-) mice was inhibited by administration of HdBc(7(d)), indicating a lack of a requirement for T and B cells in the recipient; however, depletion of macrophages in recipient mice abrogated the anti-colitic effect of HdBc(7(d)). Thus, in response to H. diminuta, a putatively unique splenic CD19(+) B cell with a functional immunoregulatory program is generated that promotes the suppression of colitis dominated by TH1, TH2, or TH1-plus-TH2 events, and may do so via the synthesis of TGF-β and the generation of, or cooperation with, a regulatory macrophage.
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada;
authors.forename: José L
authors.initials: JL
authors.lastname: Reyes
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada;
authors.forename: Arthur
authors.initials: A
authors.lastname: Wang
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada;
authors.forename: Maria R
authors.initials: MR
authors.lastname: Fernando
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada;
authors.forename: Rabea
authors.initials: R
authors.lastname: Graepel
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada;
authors.forename: Gabriella
authors.initials: G
authors.lastname: Leung
authors.affiliation: Department of Molecular Cell Biology, Vrije Universiteit Amsterdam, 1081 BT Amsterdam, the Netherlands; and.
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping 581-85, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Sigvardsson
authors.affiliation: Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Joan and Phoebe Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada; dmckay@ucalgary.ca jlreyesh@ucalgary.ca.
authors.forename: Derek M
authors.initials: DM
authors.lastname: McKay
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000096:biosynthesis; D055610:Antigens, CD1d / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D001557:Benzenesulfonates; D019013:CD40 Antigens / Q000276:immunology; D018956:CD5 Antigens / Q000096:biosynthesis; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000628:therapy; D016264:Dextran Sulfate; D018398:Homeodomain Proteins / Q000235:genetics; D006925:Hymenolepiasis / Q000276:immunology* / Q000469:parasitology; D048190:Hymenolepis diminuta / Q000276:immunology*; D056747:Immunomodulation / Q000276:immunology; D007167:Immunotherapy; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008407:Mast Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010081:Oxazolone; D017455:Receptors, IgE / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D018941:Antigens, CD19; D055610:Antigens, CD1d; D001557:Benzenesulfonates; C584692:CD1d antigen, mouse; D019013:CD40 Antigens; D018956:CD5 Antigens; C526836:Cd5 protein, mouse; D018398:Homeodomain Proteins; C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D017455:Receptors, IgE; D016212:Transforming Growth Factor beta; C007488:dinitrobenzenesulfonic acid; C064658:RAG-1 protein; D016753:Interleukin-10; D010081:Oxazolone; D015847:Interleukin-4; D016264:Dextran Sulfate