title: Maturation and function of human dendritic cells are regulated by B lymphocytes.
abstract: Mature dendritic cells (DCs) are stimulators of T-cell immune response, whereas immature DCs support T-cell tolerance. Murine B cells can inhibit the production of IL-12 by DCs and thereby hinder the inflammatory response. Notwithstanding the importance of this modulation, only a few studies are available in humans. Here, we have developed an in vitro model of cocultures to assess its significance. We establish that human activated B cells restrained the development of monocytes into immature DCs and their differentiation into mature DCs. In addition, they decreased the density of HLA-DR from mature DCs, the expression of CD80 and CD86 coactivation molecules, the production of IL-12p70 required for antigen presentation and Th1 differentiation, and inhibited the DC-induced T-cell proliferation. These modulations were mediated by CD19(+)IgD(low)CD38(+)CD24(low)CD27(-) B cells and needed direct cell-to-cell contacts that involved CD62L for the control of CD80 and CD86 expression and a soluble factor for the control of IL-12 production. Moreover, mature DCs from patients with systemic lupus erythematosus displayed insensitivity to the regulation of IL-12. Overall, it appears that human B cells can regulate DC maturation and function and that inefficient B-cell regulation may influence an improper balance between an effector inflammatory response and tolerance induction.
authors: EA2216 Immunology and Pathology, IFR 148 ScInBioS, European University of Brittany, Rennes, France.
authors: Ahsen
authors: A
authors: Morva
authors: Sébastien
authors: S
authors: Lemoine
authors: Achouak
authors: A
authors: Achour
authors: Jacques-Olivier
authors: JO
authors: Pers
authors: Pierre
authors: P
authors: Youinou
authors: Christophe
authors: C
authors: Jamin
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D018664:Interleukin-12 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D014066:Palatine Tonsil; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D006684:HLA-DR Antigens; D018664:Interleukin-12