PD-L1hi B cells are critical regulators of humoral immunity

Nat Commun. 2015 Jan 22:6:5997. doi: 10.1038/ncomms6997.

Abstract

Specific B-cell subsets can regulate T-cell immune responses, and are termed regulatory B cells (Breg). The majority of Breg cells described in mouse and man have been identified by IL-10 production and are known to suppress allergy and autoimmunity. However, Breg cell mediated immune suppression, independent of IL-10, also occurs. Here we show that Breg cells play a critical role in regulating humoral immunity mediated by CD4(+)CXCR5(+)PD-1(+) follicular helper T cells, and can suppress inflammation in autoimmune disease through elevated expression of PD-L1. We have also identified that these B cells are resistant to αCD20 B-cell depletion. This work describes how Breg cells are critical in humoral homoeostasis and may have implications for the regulation of autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Autoimmunity
  • B-Lymphocytes, Regulatory / cytology*
  • B-Lymphocytes, Regulatory / immunology
  • B7-H1 Antigen / biosynthesis*
  • B7-H1 Antigen / physiology
  • CD4-Positive T-Lymphocytes / cytology
  • Cell Differentiation
  • Cell Separation
  • Cytokines / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Homeostasis
  • Humans
  • Immune System
  • Immunity, Humoral / immunology*
  • Immunoglobulin G / immunology
  • Inflammation
  • Interleukin-10 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Programmed Cell Death 1 Receptor / metabolism*
  • Receptors, CXCR5 / metabolism
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • CD274 protein, human
  • CXCR5 protein, human
  • CXCR5 protein, mouse
  • Cd274 protein, mouse
  • Cytokines
  • Immunoglobulin G
  • PDCD1 protein, human
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Receptors, CXCR5
  • Interleukin-10