IL-12 receptor b1 deficiency alters in vivo T follicular helper cell response in humans Academic Article uri icon

Overview

MeSH Major

  • Germinal Center
  • Immunologic Memory
  • Interleukin-12
  • Receptors, Interleukin-12
  • T-Lymphocytes, Helper-Inducer

abstract

  • Antibody responses represent a key immune protection mechanism. T follicular helper (Tfh) cells are the major CD4(+) T-cell subset that provides help to B cells to generate an antibody response. Tfh cells together with B cells form germinal centers (GCs), the site where high-affinity B cells are selected and differentiate into either memory B cells or long-lived plasma cells. We show here that interleukin-12 receptor β1 (IL-12Rβ1)-mediated signaling is important for in vivo Tfh response in humans. Although not prone to B cell-deficient-associated infections, subjects lacking functional IL-12Rβ1, a receptor for IL-12 and IL-23, displayed substantially less circulating memory Tfh and memory B cells than control subjects. GC formation in lymph nodes was also impaired in IL-12Rβ1-deficient subjects. Consistently, the avidity of tetanus toxoid-specific serum antibodies was substantially lower in these subjects than in age-matched controls. Tfh cells in tonsils from control individuals displayed the active form of signal transducer and activator of transcription 4 (STAT4), demonstrating that IL-12 is also acting on Tfh cells in GCs. Thus, our study shows that the IL-12-STAT4 axis is associated with the development and the functions of Tfh cells in vivo in humans.

publication date

  • April 25, 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3637013

Digital Object Identifier (DOI)

  • 10.1182/blood-2012-08-448902

PubMed ID

  • 23476048

Additional Document Info

start page

  • 3375

end page

  • 85

volume

  • 121

number

  • 17