Kaur Kulwant, Chowdhury Shimul, Greenspan Neil S, Schreiber John R
Department of Pediatrics, University of Minnesota Medical School, Minneapolis MN 55455, USA.
Blood. 2007 Oct 15;110(8):2948-54. doi: 10.1182/blood-2007-01-069245. Epub 2007 Jul 18.
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.
与大龄儿童和成人相比，新生儿感染包膜细菌的几率更高，这是因为他们对诸如细菌多糖等非胸腺依赖性（TI）抗原的抗体反应减弱。由于肿瘤坏死因子（TNF）家族配体BAFF和APRIL与TNF家族受体（TNFRs）TACI、BCMA和BAFF-R的相互作用对TI抗体反应至关重要，我们检测了这些受体在成人及脐血来源的足月儿和早产儿新生儿B细胞上的表达。与成人B细胞相比，早产儿新生儿B细胞表达的TACI、BCMA和BAFF-R较少，并且在用人重组BAFF和抗IgM刺激后的增殖能力明显低于成人B细胞，在该实验中TACI-Fc融合蛋白可抑制B细胞增殖。此外，与成人细胞相比，新生儿树突状细胞表达的B7-1、B7-2和CD40减少。最后，新生儿B细胞，尤其是早产儿B细胞，对CD40L和IL-10的反应中IgG和IgA的产生明显减少。总体而言，这项研究表明TNFR表达的成熟延迟，尤其是早产儿新生儿B细胞的成熟延迟，可能会干扰对TI抗原的有效抗体反应、同源T细胞与B细胞的相互作用以及正常的同种型转换。
