title: Impaired function of CD19(+) CD24(hi) CD38(hi) regulatory B cells in patients with pemphigus.
abstract: BACKGROUND
  Pemphigus is an organ-specific autoimmune bullous disease.
  
  
  OBJECTIVE
  To determine the role of regulatory B cells (Bregs) in patients with pemphigus.
  
  
  METHODS
  The frequency of the occurrence of CD19(+) CD24(hi) CD38(hi) Bregs was detected from 34 patients with pemphigus and 20 healthy controls. Interleukin (IL)-10 secretion was processed after stimulating B cells. Specific antidesmoglein antibody (Ab) titres and their subclasses were also measured. Ab response and cytokine production from peripheral blood mononuclear cells (PBMCs) with or without Bregs were analysed.
  
  
  RESULTS
  The number of Bregs was significantly increased in patients with pemphigus compared with healthy controls (15 ± 7% vs. 9 ± 3%; P < 0·01) and the proportion of Bregs in the active groups (newly diagnosed and chronic active patients) was significantly higher than in remittent individuals (16 ± 7% vs. 13 ± 8%; P = 0·04). The IL-10-producing B cells were significantly increased upon stimulation both in patients and in healthy controls. However, the increase ratio of IL-10-producing B cells between short- and long-term stimulation was significantly lower in patients with pemphigus (1·0-fold vs. 2·6-fold increase in control group; P < 0·01). Strikingly, Bregs from the controls were able to suppress interferon (IFN)-γ expression and T helper cell 1 (Th1) immune response (26% inhibition rate), while the suppressive function of Bregs from patients with pemphigus was significantly decreased (9% inhibition rate). There was no difference in Ab levels from PBMCs with or without Bregs after stimulation.
  
  
  CONCLUSIONS
  Bregs in patients with pemphigus are elevated but with defective regulatory function on Th1 cells.
authors.affiliation: Department of Dermatology, Rui Jin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Dermatology, Rui Jin Hospital North, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: H-Q
authors.initials: HQ
authors.lastname: Zhu
authors.forename: R-C
authors.initials: RC
authors.lastname: Xu
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Chen
authors.forename: H-J
authors.initials: HJ
authors.lastname: Yuan
authors.forename: H
authors.initials: H
authors.lastname: Cao
authors.forename: X-Q
authors.initials: XQ
authors.lastname: Zhao
authors.forename: J
authors.initials: J
authors.lastname: Zheng
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Pan
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000502:physiology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000378:metabolism; D018941:Antigens, CD19 / Q000502:physiology*; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D051927:CD24 Antigen / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D051182:Desmogleins / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007074:Immunoglobulin G / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D010392:Pemphigus / Q000276:immunology*
chemical_list: D000906:Antibodies; D018941:Antigens, CD19; D051927:CD24 Antigen; D051182:Desmogleins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D016753:Interleukin-10; D051997:ADP-ribosyl Cyclase 1