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Reduced ability of neonatal and early-life bone marrow stromal cells to support plasmablast survival

Published in The Journal of immunology. 2006, vol. 176, no. 1, p. 165-72
Abstract In human infants (<1 year), circulating IgG Abs elicited in response to most T-dependent Ags rapidly decline and return to baseline within a few months after immunization for yet-unknown reasons. In mice immunized between 1 and 4 wk of age, a limited establishment of the bone marrow (BM) pool of long-lived plasma cells is observed. In this study, we show that tetanus toxoid (TT)-specific plasmablasts generated in the spleen are efficiently attracted in vitro and in vivo toward early-life BM stromal cells, which express adult levels of CXCL12. Similarly, adoptively transferred TT plasmablasts efficiently reach the BM compartment of 2-wk-old and adult mice. In contrast, TT plasmablasts fail to persist in the early-life BM compartment, as indicated by the persistence of a significantly lower number of TT plasmablasts in the early-life compartment than in the adult BM compartment 48 h after transfer. This limited persistence is associated with an increased rate of in vivo apoptosis of TT-specific plasmablasts that have reached the early-life BM and with a significantly lower survival rate of TT-specific plasmablasts cocultured on early-life BM stromal cells compared with adult BM stromal cells. Thus, early-life BM stromal cells fail to provide the molecular signals that support plasmablast survival and differentiation into surviving plasma cells.
Keywords Adoptive TransferAge FactorsAnimalsAnimals, NewbornApoptosis/immunologyBone Marrow Cells/immunologyCell Differentiation/immunologyChemokine CXCL12Chemokines, CXC/biosynthesisChemotaxis, Leukocyte/immunologyFlow CytometryHematopoietic Stem Cells/cytology/immunologyImmunohistochemistryMicePlasma Cells/cytology/immunologyReverse Transcriptase Polymerase Chain ReactionSpleen/cytology/immunologyStromal Cells/immunologyTetanus Toxoid/immunology
PMID: 16365407
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Research group Centre de Vaccinologie et d'Immunologie néonatale (177)
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PIHLGREN BOSCH, Maria Astrid Louise et al. Reduced ability of neonatal and early-life bone marrow stromal cells to support plasmablast survival. In: The Journal of immunology, 2006, vol. 176, n° 1, p. 165-72. doi: 10.4049/​jimmunol.176.1.165 https://archive-ouverte.unige.ch/unige:46933

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Deposited on : 2015-02-19

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