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

Elodie Belnoue, Maria Pihlgren, Tracy L. McGaha, Chantal Tougne, Anne Frangoise Rochat, Claudia Bossen, Pascal Schneider, Bertrand Huard, Paul Henri Lambert, Claire Anne Siegrist

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209 Scopus citations

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 plas-mablasts (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) El-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.

Original languageEnglish (US)
Pages (from-to)2755-2764
Number of pages10
JournalBlood
Volume111
Issue number5
DOIs
StatePublished - Mar 1 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Belnoue, E., Pihlgren, M., McGaha, T. L., Tougne, C., Rochat, A. F., Bossen, C., Schneider, P., Huard, B., Lambert, P. H., & Siegrist, C. A. (2008). APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells. Blood, 111(5), 2755-2764. https://doi.org/10.1182/blood-2007-09-110858