BIOCHEMICAL AND MOLECULAR EVENTS OF B CELL ACTIVATION BY POLYSACCHARIDES

多糖激活 B 细胞的生化和分子事件

• 批准号: 5200810
• 负责人: K A BRORSON
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200810
• 关键词: B lymphocyte; antigen antibody reaction; bacterial polysaccharides; bacterial vaccines; crosslink; cyclins; enzyme activity; gene mutation; laboratory mouse; leukocyte activation /transformation; molecular biology; protein tyrosine kinase; protooncogene

Immune responses to bacterial capsular polysaccharides involve antibody responses by B cells activated via surface Ig receptors. B cells activated by Ig cross-linking undergo an ordered chain of events. These events include stimulation of kinase activity, gene and nuclear factor activation, and entry into cell cycle. Mice with the x-linked immunodeficiency gene (xid) are believed to possess a mutation in the pleckstrin homology domain of Bruton's tyrosine kinase (Btk). These animals are unresponsive to polysaccharide antigens, moreover their B cells do not proliferate after Ig cross-linking, although they do enlarge. To determine at which point in the activation pathway xid cells become arrested, both early and late events are being compared in sIg activated xid and wildtype B cells. We have found that early G1 events, such as nuclear factor and proto-oncogene induction occur in xid cells normally. Furthermore, the activity of src related kinases was equivalent in xid and wildtype cells. However, induction of cell cycle associated events did not occur in xid cells. A clear understanding of the events associated with sIg mediated activation is required to optimize immune responses to polysaccharide vaccines because these antigens have the ability to trigger B cells directly. This understanding is especially important for vaccination of very young and elderly populations which respond poorly to polysaccharides.

对细菌荚膜多糖的免疫反应涉及抗体 B 细胞通过表面 Ig 受体激活的反应。 B细胞 由 Ig 交联激活经历一系列有序的事件。 这些 事件包括刺激激酶活性、基因和核因子 激活并进入细胞周期。 具有x连锁的小鼠 免疫缺陷基因（xid）被认为具有突变 布鲁顿酪氨酸激酶 (Btk) 的 pleckstrin 同源结构域。 这些 动物对多糖抗原没有反应，而且它们的 B Ig 交联后细胞不会增殖，但会增殖 放大。 确定 xid 细胞激活途径中的哪个点 被捕，早期和晚期事件都在 sIg 中进行比较 激活的 xid 和野生型 B 细胞。 我们发现早期的G1事件， xid细胞中发生核因子和原癌基因等诱导 通常情况下。 此外，src相关激酶的活性是 xid 和野生型细胞中的等效值。 然而，细胞周期的诱导 xid 细胞中没有发生相关事件。 清楚地了解 与 sIg 介导的激活相关的事件需要 优化对多糖疫苗的免疫反应，因为这些 抗原具有直接触发 B 细胞的能力。 这 了解对于幼儿和儿童的疫苗接种尤其重要 对多糖反应较差的老年人群。