ANTIBODY DIVERSITY IN RESPONSES TO POLYSACCHARIDE VACCIN

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，抗体谱系可以是 产生的数量要大得多，新的克隆类型的出现证明了这一点 在用多糖-蛋白质复合体免疫的小鼠中产生。这个 这项调查的重点是确定 哪些潜在的抗体实际上是被表达的。我们早些时候 免疫球蛋白抗体等电聚焦(IEF)模式的研究 在基因决定的小鼠中产生的对BL免疫的反应 菌株表明，免疫球蛋白反应的复杂性是受调节的。 至少一个C57BL/6基因，命名为谱型调节基因1 (SR1)，与IgH基因复合体、MHC或毛色无关。 正在进行的工作集中在将SR1基因定位到一只小鼠身上 染色体。一大群(BALB/c X C57BL/6)F1小鼠回交到 已培育出BALB/c，用BL1免疫，表型为SR1阳性或 IEF分析血清中抗菊粉抗体阴性。脾 已从所有回交1号(Bc1)小鼠中分离出DNA。vbl.使用 简单序列重复(SSR)-聚合酶链式反应(SSR-PCR)，对Bc1小鼠进行了基因分型 位于1至19号染色体上的遗传标记。我们的数据表明 SR1和常染色体之间的连锁，这一结果得到以下支持 CXB重组自交系的表型和基因型分析。 BC1小鼠和其他CXB菌株的基因分型正在进行中。我们 计划培育更多的Bc1小鼠，并检查其基因和表型 在我们已有的区域中缺乏C57BL/6基因的同源菌株 被确定为SR1的可能位置。TCRb/TCRd的最新研究 双基因敲除小鼠已经证实对BL的反应是一种TI 回应。调控基因(SR1)的定位与鉴定 甲型肝炎疫苗免疫后抗体多样性的表达 多糖类抗原将有助于更好地理解 多糖的免疫应答和抗体的调节 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 (Sr1 ), and is not linked to the Igh gene complex, MHC, or coat color. Work in progress is focused on mapping the Sr1 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 phenotyped as Sr1 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. Using simple sequence repeat (SSR)-PCR, the BC1 mice have been genotyped at genetic markers located on chromosomes 1 through 19. Our data indicate linkage between Sr1 and an autosome and this result is supported by phenotype and genotype analyses of CXB recombinant inbred lines. Genotyping of the BC1 mice and additional CXB strains is in progress. We plan to breed additional BC1 mice and examine the genotype and phenotype of a congenic strain which lacks C57BL/6 genes in the region we have identified as a possible location for Sr1. Recent studies with TCRb/TCRd double knockout mice have confirmed that the response to BL is a TI response. Mapping and characterization of a gene (Sr1 ) which regulates the expression of antibody diversity following immunization with a polysaccharide antigen will contribute to a betterunderstanding of the immune response to polysaccharides and of the regulation of antibody diversity.