ANTIBODY DIVERSITY IN RESPONSES TO POLYSACCHARIDE VACCINES

单糖，如细菌多糖(BL)，未与其偶联 蛋白质可引起胸腺非依赖性(TI)反应。尽管德州仪器 反应是克隆性受限的，抗体的库可以 被生产的要大得多，新的出现就是明证 多糖蛋白免疫小鼠产生的克隆型 复合体。这项调查的重点是机制或 决定哪些潜在抗体实际上是 表达。我们早期的研究考察了等电聚焦(IEF) 布氏杆菌免疫后产生的免疫球蛋白抗体模式 在基因定义的小鼠品系中证明了 免疫球蛋白反应受至少一个C57BL/6基因调控，命名为 谱型调节基因1(sr-1)，与免疫球蛋白基因无关 复合体、MHC或毛色。正在进行的工作重点是绘制 将SR-1基因克隆到小鼠染色体上。一大群(BALB/c X C57BL/6)F1 BALB/c回交小鼠经BALB/c基因分型、BALB/c基因分型和BALB/c基因分型 IEF法检测抗菊粉抗体为sr-1阳性或阴性 在血清中。已从所有回交1号中分离出脾DNA (Bc1)小鼠和一组遗传标记已经被选择用于初步的 染色体的筛选。小鼠的基因分型正在使用 简单重复序列(SSR)-聚合酶链式反应。所有选定的标记都已 对亲代小鼠品系的DNA进行了测试，大约三分之一 的标记不能用于分析。这些产品的替代者 已经选择了遗传标记，并用 来自亲本菌株的DNA目前正在进行中。血吸虫的基因分型 使用1至9号染色体上的标记的bc1小鼠已经完成 到目前为止，还没有发现sr-1与这些标记中的任何一个之间的连锁。 检测到。BC2和BC3小鼠已经被培育出来，以便在以后的分析中使用。 在第10至19号染色体上有标记的bc1小鼠的基因分型工作在 进步。利用TCRb/TCRd双基因敲除小鼠的研究进展 用BL免疫表明这些动物能产生抗体 BL和菊粉，提供了进一步的证据表明这种反应是 T细胞独立。一个基因(sr-1)的定位和特征分析 调节免疫后抗体多样性的表达 多糖类抗原有助于更好地理解 对多糖类的免疫应答和对 抗体多样性。

Simple polysaccharides, such as bacterial levan (BL), not conjugated to protein elicit a thymus independent (TI) response. Although the TI response is clonally restricted, the repertoire of antibodies that can be produced is much greater as evidenced by the appearance of new clonotypes produced in mice immunized with polysaccharide-protein complexes. The focus of this investigation is on the mechanisms or events that determine which of the potential antibodies is actually expressed. Our earlier studies examining the isoelectric focusing (IEF) pattern of IgG antibodies produced in response to immunization with BL in genetically defined mouse strains demonstrated that the complexity of the IgG response is regulated by at least one C57BL/6 gene, designated spectrotype regulation gene 1 (Sr-1), and is not linked to the Igh gene complex, MHC, or coat color. Work in progress is focused on mapping the Sr-1 gene to a murine chromosome. A large group of (BALB/c X C57BL/6)F1 mice backcrossed to BALB/c has been bred, immunized with BL, and typed as Sr-1 positive or negative by IEF analysis of anti-inulin antibodies in the serum. Spleen DNA has been isolated from all of the backcross 1 (BC1) mice and a set of genetic markers has been selected for the initial screening of the chromosomes. Genotyping of the mice is being done using simple sequence repeat (SSR)-PCR. All of the selected markers have been tested on DNA from the parental mouse strains and approximately one third of the markers were not usable for the analysis. Replacements for these genetic markers have been selected and testing of these new markers with DNA from the parental strains is currently in progress. Genotyping of the BC1 mice using markers on chromosomes 1 through 9 has been completed and thus far no linkage between Sr-1 and any of these markers has been detected. BC2 and BC3 mice have been bred to to used in later analyses. Genotyping of BC1 mice with markers on chromosomes 10 through 19 is in progress. Recent studies using TCRb/TCRd double knockout mice mice immunized with BL demonstrated that these animals produce antibodies to both BL and inulin, providing additional evidence that this response is T cell independent. Mapping and characterization of a gene (Sr-1) which regulates the expression of antibody diversity following immunization with a polysaccharide antigen will contribute to a better understanding of the immune response to polysaccharides and of the regulation of antibody diversity.