title: Decreased expression of tumor necrosis factor family receptors involved in humoral immune responses in preterm neonates.
abstract: 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.
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School, Minneapolis MN 55455, USA. kambo002@umn.edu
authors.forename: Kulwant
authors.initials: K
authors.lastname: Kaur
authors.forename: Shimul
authors.initials: S
authors.lastname: Chowdhury
authors.forename: Neil S
authors.initials: NS
authors.lastname: Greenspan
authors.forename: John R
authors.initials: JR
authors.lastname: Schreiber
mesh_terms: D000328:Adult; D000917:Antibody Formation / Q000502:physiology*; D053264:B-Cell Activating Factor / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005312:Fetal Blood; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007231:Infant, Newborn; D007234:Infant, Premature / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13