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Title

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

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Published in Journal of Clinical Investigation. 2008, vol. 118, no. 8, p. 2887-2895
Abstract 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.
Keywords Cell LineHeparan Sulfate Proteoglycans/metabolismHumansKidney/cytologyMucous Membrane/immunologyNeutrophils/metabolismPlasma Cells/immunologyTumor Necrosis Factor Ligand Superfamily Member 13/genetics/secretion
Stable URL http://archive-ouverte.unige.ch/unige:1157
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Identifiers
PMID: 18618015
Structures
Research groups Neuroprothèses sensorielles pour la restitution de l'audition et l'équilibre (268)
Groupe Anselm Wiskott-Susanne Scherrer (315)
La matrice extracellulaire (651)
Lymphomes MALT et réplication virale (807)
Analyses cellulaires et moléculaires des hémopathies malignes (929)

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Deposited on : 2009-03-17

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