title: PD-L1hi B cells are critical regulators of humoral immunity.
abstract: Specific B-cell subsets can regulate T-cell immune responses, and are termed regulatory B cells (Breg). The majority of Breg cells described in mouse and man have been identified by IL-10 production and are known to suppress allergy and autoimmunity. However, Breg cell mediated immune suppression, independent of IL-10, also occurs. Here we show that Breg cells play a critical role in regulating humoral immunity mediated by CD4(+)CXCR5(+)PD-1(+) follicular helper T cells, and can suppress inflammation in autoimmune disease through elevated expression of PD-L1. We have also identified that these B cells are resistant to αCD20 B-cell depletion. This work describes how Breg cells are critical in humoral homoeostasis and may have implications for the regulation of autoimmune diseases.
authors.affiliation: Translational Immunology Group, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Adnan R
authors.initials: AR
authors.lastname: Khan
authors.affiliation: Translational Immunology Group, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Emily
authors.initials: E
authors.lastname: Hams
authors.affiliation: Translational Immunology Group, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Achilleas
authors.initials: A
authors.lastname: Floudas
authors.affiliation: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a Joint Venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), 30625 Hanover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: Department of Pathology, University of Alabama, Birmingham, Alabama 35294-1170, USA.
authors.forename: Casey T
authors.initials: CT
authors.lastname: Weaver
authors.affiliation: 1] Translational Immunology Group, School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland [2] National Children's Research Centre, Our Lady's Children's Hospital, Dublin 12, Ireland [3] Institute of Molecular Medicine, School of Medicine St James's Hospital, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
mesh_terms: D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D015551:Autoimmunity; D060151:B-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology; D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D002469:Cell Separation; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D006706:Homeostasis; D006801:Humans; D007107:Immune System; D056724:Immunity, Humoral / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D054380:Receptors, CXCR5 / Q000378:metabolism; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C095085:CXCR5 protein, human; C513179:CXCR5 protein, mouse; C498919:Cd274 protein, mouse; D016207:Cytokines; D007074:Immunoglobulin G; C105992:PDCD1 protein, human; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D054380:Receptors, CXCR5; D016753:Interleukin-10