title: B cell subsets and dysfunction of regulatory B cells in IgG4-related diseases and primary Sjögren's syndrome: the similarities and differences.
abstract: BACKGROUND
  IgG4-related disease (IgG4-RD) is a multisystem-involved autoimmune disease. Abnormally activated and differentiated B cells may play important roles. Regulatory B cells (Breg) are newly defined B cell subgroups with immunosuppressive functions. In this study, we investigated the differences of B cell subsets, the expressions of co-stimulatory molecules on B cells, and the function of Breg cells in patients with IgG4-RD, primary Sjögren's syndrome (pSS) as well as in healthy controls (HC).
  
  
  METHODS
  Newly diagnosed IgG4-RD patients (n = 48) were enrolled, 38 untreated pSS patients and 30 healthy volunteers were recruited as disease and healthy controls. To analyze B cell subsets and B cell activity, PBMCs were surface stained and detected by flow cytometry. The function of Breg cells was tested by coculturing isolated CD19 + CD24(hi)CD38(hi) Breg cells with purified CD4 + CD25- T cells. Serum cytokines were measured by ELISA and cytometric bead array. Relationship between clinical data and laboratory findings were analyzed as well.
  
  
  RESULTS
  Compared with pSS patients and HC, IgG4-RD patients had a lower frequency of peripheral Breg cells. Interestingly, CD19 + CD24-CD38(hi) B cell subsets were significantly higher in peripheral B cells from IgG4-RD patients than in pSS patients and HC, which correlated with serum IgG4 levels. The expression of BAFF-R and CD40 on B cells was significantly lower in IgG4-RD patients compared with those in pSS patients and HC. Unlike HC, Breg cells from pSS patients lacked suppressive functions.
  
  
  CONCLUSIONS
  B cells in patients with IgG4-RD and pSS display a variety of abnormalities, including disturbed B cell subpopulations, abnormal expression of key signaling molecules, co-stimulatory molecules, and inflammatory cytokines. In addition, a significantly increased B cell subset, CD19 + CD24-CD38(hi) B cells, may play an important role in the pathogenesis of IgG4-RD.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.forename: Lixia
authors.initials: L
authors.lastname: Jin
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Wu
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Fei
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Li
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zeng
authors.forename: Fengchun
authors.initials: F
authors.lastname: Zhang
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology / Q000378:metabolism; D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D053265:B-Cell Activation Factor Receptor / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D051927:CD24 Antigen / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012859:Sjogren's Syndrome / Q000097:blood / Q000276:immunology*
chemical_list: D018941:Antigens, CD19; D053265:B-Cell Activation Factor Receptor; D051927:CD24 Antigen; D019013:CD40 Antigens; D016207:Cytokines; D007074:Immunoglobulin G; D053645:Interleukin-2 Receptor alpha Subunit; C435926:TNFRSF13C protein, human; D051997:ADP-ribosyl Cyclase 1