A T Cell-Dependent Mechanism for the Induction of Human Mucosal Homing Immunoglobulin A-Secreting Plasmablasts

Melissa Dullaers, Dapeng Li, Yaming Xue, Ling Ni, Ingrid Gayet, Rimpei Morita, Hideki Ueno, Karolina Anna Palucka, Jacques Banchereau, Sang Kon Oh

Research output: Contribution to journalArticlepeer-review

98 Citations (Scopus)

Abstract

Mucosal immunoglobulin A (IgA) secreted by local plasma cells (PCs) is a critical component of mucosal immunity. Although IgA class switching can occur at mucosal sites, high-affinity PCs are optimally generated in germinal centers (GCs) in a T cell-dependent fashion. However, how CD4+ helper T cells induce mucosal-homing IgA-PCs remains unclear. Here, we show that transforming growth factor β1 (TGFβ1) and interleukin 21 (IL-21), produced by follicular helper T cells (Tfh), synergized to generate abundant IgA-plasmablasts (PBs). In the presence of IL-21, TGFβ1 promoted naive B cell proliferation and differentiation and overrode IL-21-induced IgG class switching in favor of IgA. Furthermore, TGFβ1 and IL-21 downregulated CXCR5 while upregulating CCR10 on plasmablasts, enabling their exit from GCs and migration toward local mucosa. This was supported by the presence of CCR10+IgA+PBs in tonsil GCs. These findings show that Tfh contribute to mucosal IgA. Thus, mucosal vaccines should aim to induce robust Tfh responses.

Original languageEnglish
Pages (from-to)120-129
Number of pages10
JournalImmunity
Volume30
Issue number1
DOIs
Publication statusPublished - 2009 Jan 16

Keywords

  • CELLIMM

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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