APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells.

Details

Ressource 1Download: BIB_62E42B45EB4B.P001.pdf (853.69 [Ko])
State: Public
Version: author
Serval ID
serval:BIB_62E42B45EB4B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells.
Journal
Blood
Author(s)
Belnoue E., Pihlgren M., McGaha T.L., Tougne C., Rochat A.F., Bossen C., Schneider P., Huard B., Lambert P.H., Siegrist C.A.
ISSN
0006-4971 (Print)
ISSN-L
0006-4971
Publication state
Published
Issued date
2008
Volume
111
Number
5
Pages
2755-2764
Language
english
Abstract
The persistence of serum IgG antibodies elicited in human infants is much shorter than when such responses are elicited later in life. The reasons for this rapid waning of antigen-specific antibodies elicited in infancy are yet unknown. We have recently shown that adoptively transferred tetanus toxoid (TT)-specific plasmablasts (PBs) efficiently reach the bone marrow (BM) of infant mice. However, TT-specific PBs fail to persist in the early-life BM, suggesting that they fail to receive the molecular signals that support their survival/differentiation. Using a proliferation-inducing ligand (APRIL)- and B-cell activating factor (BAFF) B-lymphocyte stimulator (BLyS)-deficient mice, we demonstrate here that APRIL is a critical factor for the establishment of the adult BM reservoir of anti-TT IgG-secreting cells. Through in vitro analyses of PB/plasma cell (PC) survival/differentiation, we show that APRIL induces the expression of Bcl-X(L) by a preferential binding to heparan sulfate proteoglycans at the surface of CD138(+) cells. Last, we identify BM-resident macrophages as the main cells that provide survival signals to PBs and show that this function is slowly acquired in early life, in parallel to a progressive acquisition of APRIL expression. Altogether, this identifies APRIL as a critical signal for PB survival that is poorly expressed in the early-life BM compartment.
Keywords
Animals, B-Cell Activating Factor/immunology, B-Cell Activating Factor/metabolism, Bone Marrow Cells/cytology, Bone Marrow Cells/immunology, Cell Line, Cell Survival, Gene Expression Regulation, Humans, Mice, Plasma Cells/cytology, Plasma Cells/immunology, Protein Binding, Proteoglycans/metabolism, RNA, Messenger/genetics, RNA, Messenger/metabolism, Stromal Cells/cytology, Stromal Cells/immunology, Tumor Necrosis Factor Ligand Superfamily Member 13/genetics, Tumor Necrosis Factor Ligand Superfamily Member 13/immunology
Pubmed
Web of science
Open Access
Yes
Create date
19/01/2008 17:30
Last modification date
20/08/2019 14:19
Usage data