title: Regulatory IgDhi B Cells Suppress T Cell Function via IL-10 and PD-L1 during Progressive Visceral Leishmaniasis.
abstract: During visceral leishmaniasis (VL), Th1-based inflammation is induced to control intracellular parasites. Inflammation-based pathology was shown to be dampened by IL-10 and eventual programmed death 1-mediated T cell exhaustion. Cell type(s) responsible for the initiation of T cell-produced IL-10 during VL are unknown. CD19(+), CD5(-), CD1d(-), IgD(hi) regulatory B cells from healthy controls produced IL-10 in the absence of infection or stimulation, in contrast to IgD(lo/neg) B cells. IgD(hi) B cells may have a de novo versus induced regulatory program. The population of IgD(hi) B cells increased 3-fold as VL progressed. B cells from VL dogs were necessary and sufficient to suppress Th1 cell effector function. IgD(hi) B cells induced IL-10 production by T cells and IgD(lo) B cells. Blockage of B cell-specific PD-L1 restored Th1 responses. IgD(hi) regulatory B cells represent a novel regulatory B cell that may precipitate T cell exhaustion during VL.
authors.affiliation: Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA 52242;
authors.forename: Robert G
authors.identifier: 0000-0003-2713-9013
authors.initials: RG
authors.lastname: Schaut
authors.affiliation: Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA 52242;
authors.forename: Ian M
authors.initials: IM
authors.lastname: Lamb
authors.affiliation: Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA 52242;
authors.forename: Angela J
authors.identifier: 0000-0002-0432-5780
authors.initials: AJ
authors.lastname: Toepp
authors.affiliation: Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA 52242;
authors.forename: Benjamin
authors.identifier: 0000-0003-2112-4750
authors.initials: B
authors.lastname: Scott
authors.affiliation: Department of Biochemistry, Health Graduate Program, Institute of Tropical Medicine, Federal University of Rio Grande do Norte, Natal 1655, 59072-970, Brazil; Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 4365, 21045-900, Brazil;
authors.forename: Carolina O
authors.initials: CO
authors.lastname: Mendes-Aguiar
authors.affiliation: Department of Biochemistry, Health Graduate Program, Institute of Tropical Medicine, Federal University of Rio Grande do Norte, Natal 1655, 59072-970, Brazil; Center for Zoonosis, Health Secretariat, Natal 1655, 59072-970, Brazil; and.
authors.forename: Jose F V
authors.initials: JF
authors.lastname: Coutinho
authors.affiliation: Department of Biochemistry, Health Graduate Program, Institute of Tropical Medicine, Federal University of Rio Grande do Norte, Natal 1655, 59072-970, Brazil;
authors.forename: Selma M B
authors.identifier: 0000-0002-4784-9904
authors.initials: SM
authors.lastname: Jeronimo
authors.affiliation: Immunology Program, University of Iowa Carver College of Medicine, Iowa City, IA 52242.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Wilson
authors.affiliation: Immunology Program, University of Iowa Carver College of Medicine, Iowa City, IA 52242.
authors.forename: John T
authors.identifier: 0000-0001-7266-2802
authors.initials: JT
authors.lastname: Harty
authors.affiliation: Immunology Program, University of Iowa Carver College of Medicine, Iowa City, IA 52242.
authors.forename: Thomas J
authors.identifier: 0000-0001-6147-6991
authors.initials: TJ
authors.lastname: Waldschmidt
authors.affiliation: Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA 52242; Immunology Program, University of Iowa Carver College of Medicine, Iowa City, IA 52242 christine-petersen@uiowa.edu.
authors.forename: Christine A
authors.identifier: 0000-0002-7285-4254
authors.initials: CA
authors.lastname: Petersen
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D000913:Antibodies, Protozoan / Q000378:metabolism; D000953:Antigens, Protozoan / Q000276:immunology*; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000469:parasitology; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D018450:Disease Progression; D004285:Dogs; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007072:Immunoglobulin D / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008297:Male; D015800:Protozoan Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000469:parasitology
chemical_list: D019138:Antibodies, Blocking; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D060890:B7-H1 Antigen; D007072:Immunoglobulin D; D015800:Protozoan Proteins; D016753:Interleukin-10; C079253:K39 antigen, Leishmania