SUBCLASS RESPONSE TO POLYSACCHARIDE ANTIGENS IN CHILDREN

本研究旨在评估亚类分布和克隆 A组链球菌碳水化合物（GAC）抗体的多样性， 磷酸胆碱（PC）和H.流感病毒B型荚膜多糖 在正常儿童中，以及在（IgG 2）缺乏、无脾和 镰状细胞性贫血 对小鼠的研究表明， （抗PS）抗体限于特定的亚类IgG 3。 正常 婴儿小鼠和一种免疫缺陷小鼠CBA/N缺乏这种能力， 分泌这一亚类的抗体， 是由PS包裹的微生物引起的。 同样，许多人类抗PS 抗体被限制为IgG 2亚类，该亚类在哺乳动物中发展较晚。 正常儿童 此外，已经认识到IgG 2的缺陷， 反复细菌感染的儿童和成人。 我们建议 正常儿童和某些群体的易感性增加， 患者，包括无脾和SS患者，PS引起的感染 包封的细菌至少部分是由于IgG 2缺乏。 本提案中概述的研究将检查IgG 2与 这些受试者中抗PS抗体的大小和克隆多样性。 在 此外，负责增加多样性和变化的因素， 通过人抗GAC的等电聚焦观察到的克隆优势 将分析抗体。 具体而言， 将检查亚类、轻链和独特型表达。 最后，将制备对GAC和PC特异性的人杂交瘤抗体。 制作。 这些将用于研究各种功能的能力， 亚类和开发抗独特型试剂。 后者将作为 检测特定V区与IEF克隆型的关系的探针 模式，并确定，在幼儿中， 抗体分泌和V区在B细胞表面的表达。

This study is designed to assess the subclass distribution and clonal diversity of antibodies to group A streptococcal carbohydrate (GAC), phosphocholine (PC) and H. influenzae type b capsular polysaccharide (PRP) in normal children, and in children with (IgG2) deficiency, asplenia, and sickle cell anemia. Studies in mice have shown that anti-polysaccharide (anti-PS) anitbodies are restricted to a particular subclass, IgG3. Normal infant mice, and a strain of immunodeficient mice, CBA/N, lack the ability to secrete antibodies of this subclass, and are susceptible to infections caused by PS encapsulated organisms. Similarly, many human anti-PS antibodies are restricted to a subclass IgG2 which is late to develop in normal children. Further, deficiencies of IgG2 have been recognized in children and adults with recurrent bacterial infections. We propose that the increased susceptibility of normal children and certain groups of patients, including those with asplenia and SS, to infections caused by PS encapsulated bacteria is due, at least in part, to IgG2 deficiency. Studies outlined in this proposal will examine the relation of IgG2 to the magnitude and clonal diversity of anti-PS antibodies in these subjects. In addition, factors responsible for increasing diversity and changes in clonal dominance observed by isolectric focusing of human anti-GAC antibodies will be analyzed. Specifically, the contributions of subclasses, light chains and idiotype expression will be examined. Finally, human hybridoma antibodies specific for GAC and PC will be produced. These will be used to study the functional capacity of various subclasses and to develop anti-idiotype reagents. The latter will serve as probes to examine the relation of particular V regions to IEF clonotype patterns, and to determine, in young children, the relation between antibody secretion and V region expression on B cell surfaces.