Interleukin-2 inhibits germinal center formation by limiting T follicular helper cell differentiation

Immunity. 2012 May 25;36(5):847-56. doi: 10.1016/j.immuni.2012.02.012. Epub 2012 Mar 29.

Abstract

T follicular helper (Tfh) cells promote T cell-dependent humoral immune responses by providing T cell help to B cells and by promoting germinal center (GC) formation and long-lived antibody responses. However, the cellular and molecular mechanisms that control Tfh cell differentiation in vivo are incompletely understood. Here we show that interleukin-2 (IL-2) administration impaired influenza-specific GCs, long-lived IgG responses, and Tfh cells. IL-2 did not directly inhibit GC formation, but instead suppressed the differentiation of Tfh cells, thereby hindering the maintenance of influenza-specific GC B cells. Our data demonstrate that IL-2 is a critical factor that regulates successful Tfh and B cell responses in vivo and regulates Tfh cell development.

Publication types

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

MeSH terms

  • Animals
  • Antibody Formation / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Differentiation / immunology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Germinal Center / cytology
  • Germinal Center / immunology*
  • Germinal Center / metabolism
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Interleukin-2 / immunology*
  • Interleukin-2 / metabolism
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae / immunology
  • Orthomyxoviridae / metabolism
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / metabolism
  • Proto-Oncogene Proteins c-bcl-6
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Bcl6 protein, mouse
  • DNA-Binding Proteins
  • Il2ra protein, mouse
  • Immunoglobulin G
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Proto-Oncogene Proteins c-bcl-6