Impaired function of CD19(+) CD24(hi) CD38(hi) regulatory B cells in patients with pemphigus

Br J Dermatol. 2015 Jan;172(1):101-10. doi: 10.1111/bjd.13192. Epub 2014 Nov 20.

Abstract

Background: Pemphigus is an organ-specific autoimmune bullous disease.

Objectives: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / physiology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies / metabolism
  • Antigens, CD19 / physiology*
  • B-Lymphocytes, Regulatory / immunology*
  • B-Lymphocytes, Regulatory / metabolism
  • CD24 Antigen / physiology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Cells, Cultured
  • Desmogleins / immunology
  • Female
  • Humans
  • Immunity, Cellular / physiology
  • Immunoglobulin G / metabolism
  • Immunoglobulin M / metabolism
  • Interleukin-10 / biosynthesis
  • Male
  • Middle Aged
  • Pemphigus / immunology*

Substances

  • Antibodies
  • Antigens, CD19
  • CD24 Antigen
  • Desmogleins
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukin-10
  • ADP-ribosyl Cyclase 1