title: B lymphocytes and B-cell activating factor promote collagen and profibrotic markers expression by dermal fibroblasts in systemic sclerosis.
abstract: BACKGROUND
  B lymphocytes might play a pathogenic role in dermal fibrosis in systemic sclerosis (SSc). B-cell activating factor (BAFF), a key cytokine for B-cell activation, is increased in the serum and the skin of patients with SSc. However, the ability of B cells directly to stimulate dermal fibroblasts and the role of BAFF are not fully understood. We therefore investigated the involvement of B cells and BAFF in the expression of collagen and profibrotic markers by dermal fibroblasts.
  
  
  METHODS
  Cocultures of blood B cells from healthy blood donors and normal or SSc dermal fibroblasts stimulated with anti-IgM and BAFF were performed. Alpha-SMA, TIMP1, MMP9, COL1A1, COL1A2, and COL3A1 mRNA expression were determined by quantitative RT-PCR. Soluble collagen, BAFF, IL-6, IL-1β, TGF-β1, and CCL2 protein secretion were assessed.
  
  
  RESULTS
  Coculture of blood B cells and dermal fibroblasts isolated from SSc patients induced IL-6, TGF-β1, CCL2, and collagen secretion, as well as Alpha-SMA, TIMP1, and MMP9 expression in dermal fibroblasts. Transwell assays demonstrated that this induction was dependent on cell-cell contact. Addition of anti-IgM and BAFF to the coculture increased IL-6, CCL2, TGF-β1, and collagen secretion. B cell- and BAFF-induced collagen secretion was highly reduced by anti-TGF-β1 antibodies.
  
  
  CONCLUSIONS
  Our results showed for the first time a direct role of B cells on the production of collagen by dermal fibroblasts, which is further enhanced by BAFF. Thus, these results demonstrate a new pathogenic role of B cells and BAFF in fibrosis and systemic sclerosis.
authors.forename: Antoine
authors.initials: A
authors.lastname: François
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chatelus
authors.forename: Dominique
authors.initials: D
authors.lastname: Wachsmann
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.forename: Seiamak
authors.initials: S
authors.lastname: Bahram
authors.forename: Ghada
authors.initials: G
authors.lastname: Alsaleh
authors.forename: Jacques-Eric
authors.initials: JE
authors.lastname: Gottenberg
mesh_terms: D000199:Actins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology; D053264:B-Cell Activating Factor / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D003094:Collagen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000276:immunology; D009130:Muscle, Smooth / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism
chemical_list: D000199:Actins; D000888:Antibodies, Anti-Idiotypic; D053264:B-Cell Activating Factor; D018932:Chemokine CCL2; D007075:Immunoglobulin M; D015850:Interleukin-6; C560822:TIMP1 protein, human; C505719:TNFSF13B protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; C044203:anti-IgM; D003094:Collagen; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9