IgG Epitopes Processed and Presented by IgG+ B Cells Induce Suppression by Human Thymic-Derived Regulatory T Cells

J Immunol. 2021 Mar 15;206(6):1194-1203. doi: 10.4049/jimmunol.2001009. Epub 2021 Feb 12.

Abstract

We described a human regulatory T cell (Treg) population activated by IgG+ B cells presenting peptides of the heavy C region (Fc) via processing of the surface IgG underlying a model for B cell-Treg cooperation in the human immune regulation. Functionally, Treg inhibited the polarization of naive T cells toward a proinflammatory phenotype in both a cognate and a noncognate fashion. Their fine specificities were similar in healthy donors and patients with rheumatoid arthritis, a systemic autoimmune disease. Four immunodominant Fc peptides bound multiple HLA class II alleles and were recognized by most subjects in the two cohorts. The presentation of Fc peptides that stimulate Treg through the processing of IgG by dendritic cells (DC) occurred in myeloid DC classical DC 1 and classical DC 2. Different routes of Ag processing of the IgG impacted Treg expansion in rheumatoid arthritis patients.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigen Presentation
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology*
  • Dendritic Cells / immunology
  • Epitopes, B-Lymphocyte / immunology*
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immunoglobulin Fc Fragments / immunology*
  • Immunoglobulin Fc Fragments / metabolism
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Primary Cell Culture
  • T-Lymphocytes, Regulatory / immunology*
  • Young Adult

Substances

  • Epitopes, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • Immunoglobulin Fc Fragments
  • Immunoglobulin G