BIOCHEMICAL AND MOLECULAR EVENTS OF B CELL ACTIVATION BY POLYSACCHARIDES

对多糖的免疫反应，例如在细菌中发现的多糖， 胶囊或一些细菌疫苗涉及T细胞非依赖性抗体 通过IG受体交联激活的B细胞的反应。 的小鼠 XID突变株对多糖抗原无应答， 作为模型，其中T非依赖性（TI-2）激活B细胞 抗原缺乏。 它们可以用来描述所需的因素 对多糖的免疫反应。 据报道，这些老鼠 B细胞相关酪氨酸激酶基因btk的突变，导致 在TI-2中停滞，但不依赖于T（TD）或TI-1活化。 其他 xid的影响包括低血清IgG 3水平，缺失的B亚群， 细胞、LyB-5+ B细胞和较低数量的B细胞。探讨 xid突变在B细胞活化中的作用，xid中的事件和 通过IG交联在体外活化的非氧化B细胞被比较。 TI-2激活在B细胞中引发一系列事件， 在长达5天的时间过程中的时间顺序。 这些事件的范围 从与从G 0期到G1期的进展相关的信号事件到DNA 与进展为S/G2和M相关的合成和其他事件 相位 在其他实验室进行的早期研究表明， 直接信号传导事件，如PI翻转和酪氨酸 磷酸化在xid B细胞中是完整的。 我们广泛的分析表明， 显示xid B细胞中的其他信号事件，如原癌基因 和核因子诱导是完整的，与晚期事件更相关 进入细胞周期，如管家基因上调， 相对于非xid减少。 此外，我们还发现， 相对于非xid，xid B细胞培养物中的存活力降低 并且不受TI-2活化的影响。 进一步研究S/G2 将继续进入xid B细胞，包括检查细胞周期蛋白和 xid B细胞中的细胞周期蛋白依赖性激酶活性。 清醒的认识 需要与TI-2激活相关的事件来优化 多糖疫苗的免疫反应。 这是特别 对于非常年轻和老年人群的疫苗接种很重要， 对多糖的反应很差。

Immune responses to polysaccharides such as those found in bacterial capsules or some bacterial vaccines involve T cell independent antibody responses by B cells activated by Ig receptor cross-linking. Mice of the xid mutant strain are unresponsive to polysaccharide antigens and can serve as a model where activation of B cells by T independent (TI-2) antigens is deficient. They can be used to delineate factors required for immune responses to polysaccharides. These mice are reported to have a mutation in a B cell associated tyrosine kinase gene, btk, causing an arrest in TI-2 but not T dependent (TD) or TI-1 activation. Other effects of xid include low serum IgG3 levels, a missing subset of B cells, the Lyb-5+ B cells, and lower numbers of B cells. To investigate the effect of the xid mutation in B cell activation, events in xid and non-xid B cells activated in vitro by Ig crosslinking are being compared. TI-2 activation sets off a series of events in B cells, which proceed in a temporal order over a time course of up to 5 days. These events range from signaling events related to progression from G0 to G1 phase to DNA synthesis and other events associated with progression into S/G2 and M phase. Earlier studies performed in other labs have revealed that the immediate signaling events such as PI turn over and tyrosine phosphorylation are intact in xid B cells. Our extensive analysis has shown that other signaling events in xid B cells such as proto-oncogene and nuclear factor induction are intact, with late events more related to entry to cell cycle such as housekeeping gene up-regulation are diminished relative to non-xid. In addition, we find that sustained viability in culture of xid B cells is diminished relative to non-xid and is not effected by TI-2 activation. Further studies examining S/G2 entry in xid B cells will be pursued including examination of cyclin and cyclin dependent kinase activity in xid B cells. A clear understanding of the events associated with TI-2 activation is required to optimize immune responses to polysaccharide vaccines. This is especially important for vaccination of very young and elderly populations which respond poorly to polysaccharides.