title: Role of B cells in the pathogenesis of systemic sclerosis.
abstract: Systemic sclerosis (SSc) is an orphan disease characterized by progressive fibrosis of the skin and internal organs. Aside from vasculopathy and fibrotic processes, its pathogenesis involves an aberrant activation of immune cells, among which B cells seem to play a significant role. Indeed, B cell homeostasis is disturbed during SSc: the memory subset is activated and displays an increased susceptibility to apoptosis, which is responsible for their decreased number. This chronic loss of B cells enhances bone marrow production of the naïve subset that accounts for their increased number in peripheral blood. This permanent activation state can be explained mainly by two mechanisms: a dysregulation of B cell receptor (BCR) signaling, and an overproduction of B cell survival signals, B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). These disturbances of B cell homeostasis induce several functional anomalies that participate in the inflammatory and fibrotic events observed during SSc: autoantibody production (some being directly pathogenic); secretion of pro-inflammatory and pro-fibrotic cytokines (interleukin-6); direct cooperation with other SSc-involved cells [fibroblasts, through transforming growth factor-β (TGF-β) signaling, and T cells]. These data justify the evaluation of anti-B cell strategies as therapeutic options for SSc, such as B cell depletion or blockage of B cell survival signaling.
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; CHU de Lille, département de médecine interne et immunologie clinique, 59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares (sclérodermie systémique), 59000 Lille, France; FHU Immune-Mediated Inflammatory Diseases and Targeted Therapies, 59000 Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Sanges
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; CHU de Lille, Centre de biologie-pathologie-génétique, institut d'Immunologie, 59000 Lille, France.
authors.forename: T
authors.initials: T
authors.lastname: Guerrier
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; CHU de Lille, département de médecine interne et immunologie clinique, 59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares (sclérodermie systémique), 59000 Lille, France; FHU Immune-Mediated Inflammatory Diseases and Targeted Therapies, 59000 Lille, France. Electronic address: david.launay@chru-lille.fr.
authors.forename: D
authors.initials: D
authors.lastname: Launay
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; CHU de Lille, département de médecine interne et immunologie clinique, 59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares (sclérodermie systémique), 59000 Lille, France; FHU Immune-Mediated Inflammatory Diseases and Targeted Therapies, 59000 Lille, France; CHU de Lille, Centre de biologie-pathologie-génétique, institut d'Immunologie, 59000 Lille, France.
authors.forename: G
authors.initials: G
authors.lastname: Lefèvre
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; FHU Immune-Mediated Inflammatory Diseases and Targeted Therapies, 59000 Lille, France; CHU de Lille, Centre de biologie-pathologie-génétique, institut d'Immunologie, 59000 Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Labalette
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; CHU de Lille, département de médecine interne et immunologie clinique, 59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares (sclérodermie systémique), 59000 Lille, France; FHU Immune-Mediated Inflammatory Diseases and Targeted Therapies, 59000 Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Forestier
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; CHU de Lille, département de médecine interne et immunologie clinique, 59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares (sclérodermie systémique), 59000 Lille, France; FHU Immune-Mediated Inflammatory Diseases and Targeted Therapies, 59000 Lille, France.
authors.forename: V
authors.initials: V
authors.lastname: Sobanski
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; FHU Immune-Mediated Inflammatory Diseases and Targeted Therapies, 59000 Lille, France; CHU de Lille, département de rhumatologie, 59000 Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Corli
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; CHU de Lille, Centre de biologie-pathologie-génétique, institut d'Immunologie, 59000 Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Hauspie
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Jendoubi
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; FHU Immune-Mediated Inflammatory Diseases and Targeted Therapies, 59000 Lille, France; CHU de Lille, département des maladies du sang, 59000 Lille, France.
authors.forename: I
authors.initials: I
authors.lastname: Yakoub-Agha
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; CHU de Lille, département de médecine interne et immunologie clinique, 59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares (sclérodermie systémique), 59000 Lille, France; FHU Immune-Mediated Inflammatory Diseases and Targeted Therapies, 59000 Lille, France.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Hatron
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; CHU de Lille, département de médecine interne et immunologie clinique, 59000 Lille, France; Centre national de référence maladies systémiques et auto-immunes rares (sclérodermie systémique), 59000 Lille, France; FHU Immune-Mediated Inflammatory Diseases and Targeted Therapies, 59000 Lille, France.
authors.forename: E
authors.initials: E
authors.lastname: Hachulla
authors.affiliation: Université de Lille, U995, Lille Inflammation Research International Center (LIRIC), 59000 Lille, France; Inserm, U995, 59000 Lille, France; FHU Immune-Mediated Inflammatory Diseases and Targeted Therapies, 59000 Lille, France; CHU de Lille, Centre de biologie-pathologie-génétique, institut d'Immunologie, 59000 Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Dubucquoi
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D002450:Cell Communication / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D058990:Molecular Targeted Therapy; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies
keywords: B cell; BAFF; CD19; Rituximab; Systemic sclerosis