Decreased expression of tumor necrosis factor family receptors involved in humoral immune responses in preterm neonates. Blood 2007 Oct 15;110(8):2948-54
Date
07/20/2007Pubmed ID
17634409DOI
10.1182/blood-2007-01-069245Scopus ID
2-s2.0-35548967182 (requires institutional sign-in at Scopus site) 83 CitationsAbstract
Neonates have an increased rate of infection with encapsulated bacteria compared with older children and adults because of diminished antibody responses to T-independent (TI) antigens such as bacterial polysaccharides. Because the interactions of tumor necrosis factor (TNF) family ligands BAFF and APRIL with the TNF family receptors (TNFRs) TACI, BCMA, and BAFF-R are crucial to TI antibody responses, we measured the expression of these receptors on adult and cord blood-derived term and preterm neonatal B cells. Preterm neonatal B cells expressed less TACI, BCMA, and BAFF-R compared with adult B cells and had significantly less proliferation compared with adult B cells after stimulation with human recombinant BAFF and anti-IgM in an assay in which TACI-Fc fusion protein inhibits B-cell proliferation. In addition, neonatal dendritic cells had diminished expression of B7-1, B7-2, and CD40 compared with adult cells. Finally, neonatal B cells, particularly preterm B cells, exhibited markedly decreased production of IgG and IgA in response to CD40L and IL-10. Overall, this study shows that maturational delay in TNFR expression particularly by preterm neonatal B cells may interfere with effective antibody responses to TI antigens, cognate T- and B-cell interactions and normal isotype switching.
Author List
Kaur K, Chowdhury S, Greenspan NS, Schreiber JRMESH terms used to index this publication - Major topics in bold
AdultAntibody Formation
B-Cell Activating Factor
B-Lymphocytes
Cell Proliferation
Dendritic Cells
Enzyme-Linked Immunosorbent Assay
Fetal Blood
Flow Cytometry
Gene Expression
Humans
Immunoglobulin A
Immunoglobulin G
Infant, Newborn
Infant, Premature
Lymphocyte Activation
Receptors, Tumor Necrosis Factor
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes
Tumor Necrosis Factor Ligand Superfamily Member 13