Scientific article
Open access

APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa

Published inThe Journal of clinical investigation, vol. 118, no. 8, p. 2887-2895
Publication date2008

The bone marrow constitutes a favorable environment for long-lived antibody-secreting plasma cells, providing blood-circulating antibody. Plasma cells are also present in mucosa-associated lymphoid tissue (MALT) to mediate local frontline immunity, but how plasma cell survival there is regulated is not known. Here we report that a proliferation-inducing ligand (APRIL) promoted survival of human upper and lower MALT plasma cells by upregulating expression of the antiapoptotic proteins bcl-2, bcl-xL, and mcl-1. The in situ localization of APRIL was consistent with such a prosurvival role in MALT. In upper MALT, tonsillar epithelium produced APRIL. Upon infection, APRIL production increased considerably when APRIL-secreting neutrophils recruited from the blood infiltrated the crypt epithelium. Heparan sulfate proteoglycans (HSPGs) retained secreted APRIL in the subepithelium of the infected zone to create APRIL-rich niches, wherein IgG-producing plasma cells accumulated. In lower MALT, neutrophils were the unique source of APRIL, giving rise to similar niches for IgA-producing plasmocytes in villi of lamina propria. Furthermore, we found that mucosal humoral immunity in APRIL-deficient mice is less persistent than in WT mice. Hence, production of APRIL by inflammation-recruited neutrophils may create plasma cell niches in MALT to sustain a local antibody production.

  • Cell Line
  • Heparan Sulfate Proteoglycans/metabolism
  • Humans
  • Kidney/cytology
  • Mucous Membrane/immunology
  • Neutrophils/metabolism
  • Plasma Cells/immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 13/genetics/secretion
Citation (ISO format)
HUARD, Bertrand et al. APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa. In: The Journal of clinical investigation, 2008, vol. 118, n° 8, p. 2887–2895. doi: 10.1172/JCI33760
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Article (Accepted version)
Secondary files (1)
ISSN of the journal0021-9738

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