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, SangKon Oh

Research output: Contribution to journalArticle

88 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
Externally publishedYes

Fingerprint

Immunoglobulin A
T-Lymphocytes
Germinal Center
Transforming Growth Factors
Plasma Cells
Immunoglobulin Class Switching
Mucosal Immunity
Palatine Tonsil
Cell Differentiation
Mucous Membrane
B-Lymphocytes
Down-Regulation
Vaccines
Immunoglobulin G
Cell Proliferation
interleukin-21

Keywords

  • CELLIMM

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

A T Cell-Dependent Mechanism for the Induction of Human Mucosal Homing Immunoglobulin A-Secreting Plasmablasts. / Dullaers, Melissa; Li, Dapeng; Xue, Yaming; Ni, Ling; Gayet, Ingrid; Morita, Rimpei; Ueno, Hideki; Palucka, Karolina Anna; Banchereau, Jacques; Oh, SangKon.

In: Immunity, Vol. 30, No. 1, 16.01.2009, p. 120-129.

Research output: Contribution to journalArticle

Dullaers, M, Li, D, Xue, Y, Ni, L, Gayet, I, Morita, R, Ueno, H, Palucka, KA, Banchereau, J & Oh, S 2009, 'A T Cell-Dependent Mechanism for the Induction of Human Mucosal Homing Immunoglobulin A-Secreting Plasmablasts', Immunity, vol. 30, no. 1, pp. 120-129. https://doi.org/10.1016/j.immuni.2008.11.008
Dullaers, Melissa ; Li, Dapeng ; Xue, Yaming ; Ni, Ling ; Gayet, Ingrid ; Morita, Rimpei ; Ueno, Hideki ; Palucka, Karolina Anna ; Banchereau, Jacques ; Oh, SangKon. / A T Cell-Dependent Mechanism for the Induction of Human Mucosal Homing Immunoglobulin A-Secreting Plasmablasts. In: Immunity. 2009 ; Vol. 30, No. 1. pp. 120-129.
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