Halista S M, Johnson-Robbins L A, El-Mohandes A E, Lees A, Mond J J, Katona I M
Department of Pediatrics, Uniformed Services University of the Health Sciences, F. Edward Herbert School of Medicine, Bethesda, Maryland 20814, USA.
Pediatr Res. 1998 Apr;43(4 Pt 1):496-503. doi: 10.1203/00006450-199804000-00010.
Human neonates are immunologically immature, particularly in their humoral antibody responses to T cell-independent antigens, as exemplified by their increased susceptibility to infections with polysaccharide-encapsulated bacteria. To clarify the mechanism(s) underlying the unresponsiveness of neonates to polysaccharide antigens, we used an in vitro model with neonatal cord blood cells that has been shown to mimic surface Ig-dependent signaling in the adult by T cell-independent antigens. We studied the ability of cord blood human B cells to become activated after ligation of their surface Ig by unconjugated anti-Ig, dextran-conjugated anti-Ig, and Staphylococcus aureus Cowan A1, and compared their response with that of adult B cells. After the addition of nanogram concentrations of anti-Ig-dextran, neonatal cord blood B cells proliferated at levels comparable to that observed with adult B cells. The majority of cord blood B cells showed a marked rise in intracellular calcium, increased surface expression of human leukocyte antigen DR, and an increase in cell size. Direct activation of protein kinase C by phorbol esters in neonatal B cells led to cellular proliferation, and when combined with anti-Ig, a synergistic effect on proliferation was observed. These data suggest that the unresponsiveness of human neonates to polysaccharide antigens does not represent an inability of these antigens to induce early activation events in circulating B cells.
人类新生儿在免疫方面不成熟，尤其是在对非T细胞依赖性抗原的体液抗体反应中，这表现为他们对多糖包膜细菌感染的易感性增加。为了阐明新生儿对多糖抗原无反应性的潜在机制，我们使用了一种体外模型，该模型采用新生儿脐带血细胞，已证明其可模拟成人中由非T细胞依赖性抗原介导的表面Ig依赖性信号传导。我们研究了脐带血人类B细胞在其表面Ig被未偶联的抗Ig、葡聚糖偶联的抗Ig和金黄色葡萄球菌考恩A1连接后被激活的能力，并将它们的反应与成人B细胞的反应进行比较。在加入纳克浓度的抗Ig-葡聚糖后，新生儿脐带血B细胞的增殖水平与成人B细胞相当。大多数脐带血B细胞显示细胞内钙显著升高、人类白细胞抗原DR的表面表达增加以及细胞大小增加。佛波酯对新生儿B细胞中蛋白激酶C的直接激活导致细胞增殖，并且当与抗Ig联合使用时，观察到对增殖的协同作用。这些数据表明，人类新生儿对多糖抗原的无反应性并不意味着这些抗原无法在循环B细胞中诱导早期激活事件。
