DEVELOPMENT OF ANTIBODY REPERTOIRES TO POLYSACCHARIDES

对包裹细菌感染的保护性免疫是介导性的 主要是通过对其被膜多糖(CP)的抗体(Ab)。这个 人类对这种被包裹的细菌的CP的抗体谱系通常是 在多样性方面受到高度限制，使用数量有限的 免疫球蛋白重链可变区和轻链可变区 区(V/L)基因。人抗体应答的个体发育 B型流感嗜血杆菌(Hib)Hib和多重肺炎球菌CP 延迟在婴儿，这是感染风险最高的年龄 被包裹的细菌。个体发育延迟的机制是 未知。我们假设造成这一延迟的因素是不充分的 特定V基因的表达和N区的添加，是一个过程 酶末端介导的非模板核苷酸加成反应 脱氧核苷酸转移酶。N区加成在个体发育中的延迟 在小鼠，特别是在小鼠CD5阳性的B细胞中， 与小鼠抗CP抗体的产生有关。这项提议的目的是 目的是：1)确定新生儿的kappa轻链变量 地区(Vkappa)曲目与成人曲目相比存在偏差；2) 确定Vkappa-Jkappa的N区加成的个体发育 结合点；3)开发定义人CP抗体谱系的方法。 这些结果应该为人类抗体反应的个体发育提供洞察力。 以及开发疫苗以防止细菌感染的背景 在婴儿身上。

Protective immunity to infection from encapsulated bacteria is mediated predominantly by antibody (Ab) to their capsular polysaccharide (CP). The human Ab repertoire to the CP of such encapsulated bacteria is often highly restricted in diversity with use of a limited number of immunoglobulin heavy chain variable region (V/H) and light chain variable region (V/L) genes. The ontogeny of the human Ab response to the Haemophilus influenzae type b (Hib) Hib and multiple pneumococcal CP are delayed in the infant, which is the age of highest risk of infection with encapsulated bacteria. The mechanism of this delay in ontogeny is unknown. We hypothesize that contributing to this delay are poor expression of particular V genes and of N region addition, a process of nontemplated nucleotide addition mediated by the enzyme terminal deoxynucleotidyl transferase. N region addition is delayed in ontogeny in the mouse and particularly in murine CD5 positive B cells, which have been implicated in murine Ab production to CP. The aims of this proposal are to: 1) determine whether the neonate's kappa light chain variable region (Vkappa) repertoire is skewed compared to the adult's; 2) determine the ontogeny of N region addition at the Vkappa-Jkappa junction; 3) develop approaches to defining human Ab repertoires to CP. The results should provide insights into ontogeny of human Ab responses and a background for developing vaccines to prevent bacterial infections in infants.