Decreased expression of tumor necrosis factor family receptors involved in humoral immune responses in preterm neonates
Decreased expression of tumor necrosis factor family receptors involved in humoral immune responses in preterm neonates
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DOI：
10.1182/blood-2007-01-069245
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发表时间：
2007-10-15
期刊：
影响因子：
20.3
通讯作者：
Schreiber, John R.
中科院分区：
文献类型：
--
作者：
Kaur, Kulwant;Chowdhury, Shimul;Schreiber, John R.
与年龄较大的儿童和成人相比，新生儿感染包囊细菌的比率增加，因为对T非依赖性（TI）抗原（如细菌多糖）的抗体应答减少。由于肿瘤坏死因子（TNF）家族配体BAFF和APRIL与TNF家族受体（TNFR）TACI、BCMA和BAFF-R的相互作用对TI抗体应答至关重要，因此我们测量了这些受体在成人和脐带血衍生的足月和早产新生儿B细胞上的表达。在一项TACI-Fc融合蛋白抑制B细胞增殖的试验中，与成人B细胞相比，早产新生儿B细胞表达较少的TACI、BCMA和BAFF-R，并且在用人重组BAFF和抗IgM刺激后，与成人B细胞相比，其增殖显著较少。此外，与成人细胞相比，新生儿树突状细胞B7-1、B7-2和CD 40的表达减少。最后，新生儿B细胞，特别是早产儿B细胞，表现出对CD 40 L和IL-10应答的IgG和伊加产生显著减少。总之，这项研究表明，TNFR表达的成熟延迟，特别是早产新生儿B细胞的表达可能会干扰有效的抗体应答TI抗原，同源T-和B-细胞的相互作用和正常的同种型转换。
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.