Signal Transduction in B cell Activation

B 细胞激活中的信号转导

• 批准号: 6509814
• 负责人: John C Cambier
• 金额: $ 38.03万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 2003-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6509814
• 关键词: B cell receptor; B lymphocyte; anergy; antigen receptors; biological signal transduction; genetically modified animals; immunoglobulin M; laboratory mouse; leukocyte activation /transformation; phosphorylation; protein tyrosine kinase; tissue /cell culture

DESCRIPTION (provided by applicant): A critical feature of the immune system is its ability to distinguish between self and nonself seemingly ignoring self antigens while responding to and eliminating potential pathogens. Failure of this discrimination can result in autoimmunity. While, auto-reactive antigen receptors are clearly encoded in the genome, cells expressing these receptors are silenced by a variety of mechanisms. In the B cell compartment this occurs by antigen induced editing of receptors to change specificity, deletion by apoptosis, anergy and CD5 dependent hyporesponsiveness In the latter two cases, cells remain viable and competent to bind antigen, but antigen receptor signaling is altered. The long-term objectives of the application are to elucidate the molecular mechanisms underlying the antigen hyporesponsiveness of anergic B cells and peritoneal CD5+ cells. Specific Aims are to elucidate the biochemical underpinning and biological functions of three specific mechanisms of signal modulation revealed by studies conducted during the last funding period. Two of these mechanisms, active in anergic B cells, involve (1) destabilization of the antigen receptor preventing normal transmission of signals from membrane immunoglobulin to Ig-alpha/Ig-beta dimers which function as the receptor's transmembrane transducer, and (2) activation of a negative feedback regulatory loop involving the inositol 5 phosphatase SHIP and the linker Downstream of kinase, Dok. A third mechanism, apparently operative only in peritoneal CD5+ cells, is an inhibitory loop involving Lck, CD5 and SHP-2 and targets BLNK (SLP-65). The proposed studies will be pursued using multiple lymphoma and animal models, but will rely principally on the newly described Ars/A 1 transgenic model of anergy and the VH 11 VK9 transgenic model of CD5+ B 1 cells. They will involve genetic manipulation and a variety of biochemical and biological assays of signal transduction and cellular responses. These studies may reveal drug discovery targets for autoimmunity and immunodeficiency.

描述（由申请人提供）：免疫系统的一个关键特征是

项目成果

Increase in the intracellular free calcium concentration is not an obligatory early event in lipopeptide-induced B-cell activation.

细胞内游离钙浓度的增加并不是脂肽诱导的 B 细胞活化的必然早期事件。

• 发表时间: 1991
• 期刊: Immunology
• 影响因子: 6.4
• 作者: Hauschildt,S;Luckhoff,A;Langhorne,J;Wiesmuller,KH;Jung,G;Bessler,W;Cambier,JC
• 通讯作者: Cambier,JC

Transmembrane signaling in T lymphocyte dependent B lymphocyte activation.

T 淋巴细胞依赖性 B 淋巴细胞激活中的跨膜信号传导。

• 发表时间: 1989
• 期刊: Seminars in immunology
• 影响因子: 7.8
• 作者: Cambier,JC

Modeling of T cell contact-dependent B cell activation. IL-4 and antigen receptor ligation primes quiescent B cells to mobilize calcium in response to Ia cross-linking.

T 细胞接触依赖性 B 细胞激活的建模。

• 发表时间: 1991
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Cambier,JC;Morrison,DC;Chien,MM;Lehmann,KR
• 通讯作者: Lehmann,KR

Structural compartmentalization of MHC class II signaling function.

MHC II 类信号传导功能的结构划分。

• DOI: 10.1016/0167-5699(93)90184-m
• 发表时间: 1993
• 期刊: Immunology today
• 作者: Wade,WF;Davoust,J;Salamero,J;Andre,P;Watts,TH;Cambier,JC
• 通讯作者: Cambier,JC

Alpha-chains of IgM and IgD antigen receptor complexes are differentially N-glycosylated MB-1-related molecules.

IgM 和 IgD 抗原受体复合物的 α 链是差异 N-糖基化的 MB-1 相关分子。

• 发表时间: 1991
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Campbell,KS;Hager,EJ;Cambier,JC
• 通讯作者: Cambier,JC