Submitted January 25, 2007
Accepted July 13, 2007
Decreased expression of tumor necrosis factor family receptors involved in humoral immune responses in preterm neonates
Kulwant Kaur*, Shimul Chowdhury, Neil S Greenspan, and John R Schreiber
Department of Pediatrics, University of Minnesota Medical School and the University of Minnesota Children's Hospital, Minneapolis, MN, United States
Department of Pathology, Case Western Reserve University, Cleveland, OH, United States
* Corresponding author; email: kambo002{at}umn.edu.
Neonates have an increased rate of infection with encapsulated bacteria compared to older children and adults due to diminished antibody responses to T independent (TI) antigens such as bacterial polysaccharides. Since the interactions of tumor necrosis factor (TNF) family ligands BAFF and APRIL with the TNF family receptors (TNFR) 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 to adult B cells, and had significantly less proliferation compared to 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 to 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.
