Human Extrafollicular CD4+ Th Cells Help Memory B Cells Produce Igs

J Immunol. 2018 Sep 1;201(5):1359-1372. doi: 10.4049/jimmunol.1701217. Epub 2018 Jul 20.

Abstract

Follicular helper T (Tfh) cells are necessary for germinal center B cell maturation during primary immune responses; however, the T cells that promote humoral recall responses via memory B cells are less well defined. In this article, we characterize a human tonsillar CD4+ T cell subset with this function. These cells are similar to Tfh cells in terms of expression of the chemokine receptor CXCR5 and the inhibitory receptor PD-1, IL-21 secretion, and expression of the transcription factor BCL6; however, unlike Tfh cells that are located within the B cell follicle and germinal center, they reside at the border of the T cell zone and the B cell follicle in proximity to memory B cells, a position dictated by their unique chemokine receptor expression. They promote memory B cells to produce Abs via CD40L, IL-10, and IL-21. Our results reveal a unique extrafollicular CD4+ T cell subset in human tonsils, which specialize in promoting T cell-dependent humoral recall responses.

Publication types

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

MeSH terms

  • Adolescent
  • Antibody Formation*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Child
  • Child, Preschool
  • Cytokines / immunology
  • Female
  • Gene Expression Regulation / immunology
  • Humans
  • Immunoglobulin G / immunology*
  • Immunologic Memory*
  • Male
  • Programmed Cell Death 1 Receptor / immunology
  • Proto-Oncogene Proteins c-bcl-6 / immunology
  • Receptors, CXCR5 / immunology
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • BCL6 protein, human
  • CXCR5 protein, human
  • Cytokines
  • Immunoglobulin G
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Proto-Oncogene Proteins c-bcl-6
  • Receptors, CXCR5