B LYMPHOCYTE TOLERANCE IN HEALTH AND AUTOIMMUNITY

描述(改编自调查者摘要)：这是一项研究 研究B淋巴细胞耐受性的项目资助。调查员和其他人 已经证明，在没有T细胞帮助的情况下，B细胞可以有效地 被容忍了。尽管这些研究帮助证明了B细胞 容忍可以而且确实是通过许多机制发生的，这种积累 关于B细胞耐受性的知识使一组新的 问题。与从最近的容忍中得出的一般性结论形成对比 研究表明，也有大量证据表明，自身反应性B- 细胞不能只存在于外围，特别是在B-1 但这种自我反应性实际上可以增加它们的丰度。一个 进一步反驳了多价抗原引起B- 在没有T细胞帮助的情况下细胞删除是T- 独立的抗体反应，其中高度多价的抗原 缺乏T细胞表位可有效刺激抗体反应。最后， 研究人员在B细胞耐受性方面的信息并不真正允许 以预测B细胞耐受规则在挑战过程中如何变化 有交叉反应的抗原。换句话说，他们不知道B细胞 免疫反应(如感染)中的自身反应是正常的， 也不知道这种自动反应在多大程度上是在 感染以及这些机制中是否有任何机制存在缺陷的自身免疫倾向 老鼠。了解区分积极的规则是很重要的 来自消极选择。在这份申请中，调查员的建议 B细胞在免疫消退期间和解体后的耐受性 对外来抗原的反应。为了实现这一目标，他们利用 抗体结合部位的简并性 给免疫系统带来了抗原模仿的问题。怎么了？ 免疫系统维持自我与非自我的区别 已在此应用程序中寻址。这些研究的长期目标是 了解如何避免B细胞自身反应并确定发生了什么 自动豁免权是错误的。

DESCRIPTION (Adapted from Investigator's abstract): This is a research project grant to study B lymphocyte tolerance. The investigator and others have shown that in the absence of T-cell help, B-cells can be efficiently tolerized. Although these studies have helped demonstrated that B-cell tolerance can and does occur by a number of mechanisms, this accumulating knowledge about B-cell tolerance has brought into focus a new set of questions. In contrast to the generalities concluded from recent tolerance studies, there also exists a body of evidence arguing that autoreactive B- cells cannot only persist in the periphery, particularly in the B-1 subset., but that self-reactivity can actually enhance their abundance. A further contradiction to the concept that multivalent antigens elicit B- cell deletion in the absence of T-cell help is the phenomenon of T- independent antibody responses, in which highly multivalent antigens that lack T-cell epitopes efficiently stimulate antibody responses. Finally, the investigator's information in B-cell tolerance does not really permit them to predict how the rules of B-cell tolerance change during challenge with cross reactive antigens. In other words, they do not know if B-cell autoreactivity during an immune response such as infection is the norm, nor is it known to what extent this autoreactivity is resolved after infection and if any of these mechanisms are defective in autoimmune-prone mice. It is important to understand the rules that distinguish positive from negative selection. In this application, the investigator's propose to characterize B-cell tolerance during and upon resolution of an immune response to foreign antigen. To accomplish this aim, they take advantage of a system in which the degeneracy of the antibody combining site presents a problem of antigenic mimicry to the immune system. How the immune system maintains the distinction between self and non-self will be addressed in this application. The long term goal of these studies is to understand how B-cell autoreactivity is avoided and to determine what goes wrong in autoimmunity.