TY - JOUR
T1 - APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells
AU - Belnoue, Elodie
AU - Pihlgren, Maria
AU - McGaha, Tracy L.
AU - Tougne, Chantal
AU - Rochat, Anne Frangoise
AU - Bossen, Claudia
AU - Schneider, Pascal
AU - Huard, Bertrand
AU - Lambert, Paul Henri
AU - Siegrist, Claire Anne
PY - 2008/3/1
Y1 - 2008/3/1
N2 - 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-XL 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.
AB - 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-XL 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.
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U2 - 10.1182/blood-2007-09-110858
DO - 10.1182/blood-2007-09-110858
M3 - Article
C2 - 18180376
AN - SCOPUS:41949138741
SN - 0006-4971
VL - 111
SP - 2755
EP - 2764
JO - Blood
JF - Blood
IS - 5
ER -