A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts

Immunity. 2009 Jan 16;30(1):120-9. doi: 10.1016/j.immuni.2008.11.008.


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 beta1 (TGFbeta1) 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, TGFbeta1 promoted naive B cell proliferation and differentiation and overrode IL-21-induced IgG class switching in favor of IgA. Furthermore, TGFbeta1 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • B-Lymphocytes / immunology
  • Cell Differentiation
  • Cell Proliferation
  • Chemotaxis, Leukocyte*
  • Child
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoglobulin A / classification
  • Immunoglobulin A / metabolism*
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Interleukins / physiology
  • Mucous Membrane / immunology*
  • Plasma Cells / immunology*
  • Polymerase Chain Reaction
  • Receptors, CCR10 / metabolism
  • Receptors, CXCR5 / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Reference Standards
  • T-Lymphocytes / immunology*
  • Transforming Growth Factor beta1 / physiology
  • Up-Regulation


  • CCR10 protein, human
  • CXCR5 protein, human
  • Immunoglobulin A
  • Interleukin-2
  • Interleukins
  • Receptors, CCR10
  • Receptors, CXCR5
  • Recombinant Proteins
  • Transforming Growth Factor beta1
  • interleukin-21