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

Details

Ressource 1Download: 107. Huard et al.pdf (867.37 [Ko])
State: Public
Version: author
License: Not specified
Serval ID
serval:BIB_D39B0F6B4F25
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa.
Journal
Journal of Clinical Investigation
Author(s)
Huard B., McKee T., Bosshard C., Durual S., Matthes T., Myit S., Donze O., Frossard C., Chizzolini C., Favre C., Zubler R., Guyot J.P., Schneider P., Roosnek E.
ISSN
0021-9738 (Print)
ISSN-L
0021-9738
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
118
Number
8
Pages
2887-2895
Language
english
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 Line, Heparan Sulfate Proteoglycans/metabolism, Humans, Kidney/cytology, Mucous Membrane/immunology, Neutrophils/metabolism, Plasma Cells/immunology, Tumor Necrosis Factor Ligand Superfamily Member 13/genetics, Tumor Necrosis Factor Ligand Superfamily Member 13/secretion
Pubmed
Web of science
Open Access
Yes
Create date
13/02/2009 19:37
Last modification date
18/01/2020 7:10
Usage data