Reduced ability of neonatal and early-life bone marrow stromal cells to support plasmablast survival.
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.
Pihlgren
Maria
M
World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, Department of Pathology-Immunology, University of Geneva, Geneva, Switzerland.
Friedli
Mathieu
M
Tougne
Chantal
C
Rochat
Anne-Françoise
AF
Lambert
Paul-Henri
PH
Siegrist
Claire-Anne
CA
D019264:Adoptive Transfer; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D013745:Tetanus Toxoid