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 Blood, 15 October 2007, Vol. 110, No. 8, pp. 2948-2954.
Prepublished online as a Blood First Edition Paper on July 18, 2007; DOI 10.1182/blood-2007-01-069245.

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IMMUNOBIOLOGY

Decreased expression of tumor necrosis factor family receptors involved in humoral immune responses in preterm neonates

Kulwant Kaur1,2, Shimul Chowdhury1,2, Neil S. Greenspan3, and John R. Schreiber1,3

1 Department of Pediatrics, University of Minnesota Medical School, Minneapolis; 2 University of Minnesota Children's Hospital, Fairview, Minneapolis; and 3 Department of Pathology, Case Western Reserve University, Cleveland, OH

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.


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