Positive and negative selection during B lymphocyte development

Positive and negative selection during B lymphocyte development
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DOI:
10.1385/ir:27:2-3:427
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发表时间:
2003-01-01
影响因子:
4.4
通讯作者:
Sater, R
Sater, R
中科院分区:
医学4区
文献类型:
--
作者:
Monroe, JG;Bannish, G;Sater, R

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我们的实验室对与淋巴细胞发育相关的各种问题感兴趣。更具体地说,我们重点关注调节 B 淋巴细胞 (B 细胞) 谱系决定的过程,以及参与维持 B 细胞谱系这种承诺的后续信号。这些信号导致正确选择那些正确执行与 B 细胞发育相关的复杂遗传变化的 B 细胞,然后触发对自身抗原有反应的 B 细胞的消除,因此具有介导自身免疫性疾病的潜力。我们的一般实验方法是从信号转导的角度解决这些问题。我们的目标是定义整合的生化和遗传过程,以完成这些选择过程。为此,我们采用体内动物模型以及更明确的体外研究,使用原代细胞系和转化细胞系。在过去的几年里,我们主要感兴趣的是 B 细胞抗原受体 (BCR) 以及该受体的中间形式调节这些复杂发育过程的精确机制。我们使用下面描述的正在进行的研究作为我们如何处理这些问题的两个代表性例子以及我们所取得的一些见解。为了将这两项研究放在背景中,我们将首先简要介绍 B 细胞发育。
Our laboratory is interested in a variety of issues related to lymphocyte development. More specifically, we have focused on the processes that regulate the decision to commit to the B lymphocyte (B cell) lineage, then the subsequent signals that are involved in maintaining this commitment to the B cell lineage. These signals result in the positive selection of those B cells that properly execute the complex genetic changes associated with B cell development, then trigger the elimination of B cells that are responsive to self-antigens and, therefore, possess the potential to mediate autoimmune disease. Our general experimental approach has been to address these issues from the perspective of signal transduction. Our goal is to define the biochemical and genetic processes that are integrated in order to accomplish these selection processes. To do so, we employ in vivo animal models as well as more defined in vitro studies, using both primary and transformed cell lines. For the past several years, we have been primarily interested in the precise mechanisms by which the B cell antigen receptor (BCR), and intermediate forms of this receptor, regulate these complex developmental processes. We have used the ongoing studies described below as two representative examples of how we are approaching these issues and some of the insights that we have made. To place both of these studies in context, we will begin with a brief introduction into B cell development.