BIOCHEMICAL AND MOLECULAR EVENTS OF B CELL ACTIVATION BY POLYSACCHARIDES

对细菌被膜多糖的免疫应答涉及抗体 B细胞通过表面Ig受体激活的反应。B细胞 由Ig激活的交联会经历一系列有序的事件。这些 事件包括对激酶活性、基因和核因子的刺激 激活，并进入细胞周期。带有X连锁基因的小鼠 免疫缺陷基因(Xid)被认为在 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 细胞在免疫球蛋白交联后不会增殖，尽管它们确实会 放大。确定XID细胞在激活途径中的哪个点 被逮捕，在SIG中正在比较早期和晚期事件 激活XID和野生型B细胞。我们发现早期的G1事件， 如核因子和原癌基因诱导在XID细胞中发生 通常是这样的。此外，src相关激酶的活性是 在XID和通配类型单元格中等效。然而，对细胞周期的诱导 XID单元格中未发生关联事件。对……的清醒认识 与SIG介导的激活相关的事件需要 优化对多糖疫苗的免疫应答，因为这些 抗原具有直接触发B细胞的能力。这 了解这一点对于接种非常年轻和 对多糖反应差的老年人群。

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.