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

(2009) IMMUNITY. 30(1). p.120-129
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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 beta 1 (TGF beta 1) 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, TGF beta 1 promoted naive B cell proliferation and differentiation and overrode IL-21-induced IgG class switching in favor of IgA. Furthermore, TGF beta 1 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.
Keywords
TRANSCRIPTIONAL REGULATION, COMMENSAL BACTERIA, GERMINAL CENTER, DENDRITIC CELLS, IMMUNE-RESPONSES, IGA-PRODUCING CELLS, HUMAN B-CELLS, FOLLICULAR-HELPER-CELLS, CCR10 EXPRESSION, LAMINA PROPRIA

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Chicago
Dullaers, Melissa, Dapeng Li, Yaming Xue, Ling Ni, Ingrid Gayet, Rimpei Morita, Hideki Ueno, Karolina Anna Palucka, Jacques Banchereau, and SangKon Oh. 2009. “A T Cell-dependent Mechanism for the Induction of Human Mucosal Homing Immunoglobulin A-secreting Plasmablasts.” Immunity 30 (1): 120–129.
APA
Dullaers, M., Li, D., Xue, Y., Ni, L., Gayet, I., Morita, R., Ueno, H., et al. (2009). A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts. IMMUNITY, 30(1), 120–129.
Vancouver
1.
Dullaers M, Li D, Xue Y, Ni L, Gayet I, Morita R, et al. A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts. IMMUNITY. 2009;30(1):120–9.
MLA
Dullaers, Melissa, Dapeng Li, Yaming Xue, et al. “A T Cell-dependent Mechanism for the Induction of Human Mucosal Homing Immunoglobulin A-secreting Plasmablasts.” IMMUNITY 30.1 (2009): 120–129. Print.
@article{1227900,
  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 beta 1 (TGF beta 1) 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, TGF beta 1 promoted naive B cell proliferation and differentiation and overrode IL-21-induced IgG class switching in favor of IgA. Furthermore, TGF beta 1 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.},
  author       = {Dullaers, Melissa and Li, Dapeng and Xue, Yaming and Ni, Ling and Gayet, Ingrid and Morita, Rimpei and Ueno, Hideki and Palucka, Karolina Anna and Banchereau, Jacques and Oh, SangKon},
  issn         = {1074-7613},
  journal      = {IMMUNITY},
  keyword      = {TRANSCRIPTIONAL REGULATION,COMMENSAL BACTERIA,GERMINAL CENTER,DENDRITIC CELLS,IMMUNE-RESPONSES,IGA-PRODUCING CELLS,HUMAN B-CELLS,FOLLICULAR-HELPER-CELLS,CCR10 EXPRESSION,LAMINA PROPRIA},
  language     = {eng},
  number       = {1},
  pages        = {120--129},
  title        = {A T cell-dependent mechanism for the induction of human mucosal homing immunoglobulin A-secreting plasmablasts},
  url          = {http://dx.doi.org/10.1016/j.immuni.2008.11.008},
  volume       = {30},
  year         = {2009},
}

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