REGULATORY MECHANISMS IN NORMAL AND NEOPLASTIC CELLS

正常细胞和肿瘤细胞的调节机制

基本信息

批准号：
2059971
负责人：
MALCOLM L GEFTER
金额：
$ 12.1万
依托单位：
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
1976
资助国家：
美国
起止时间：
1976-04-01 至 1994-09-30
项目状态：
已结题

项目摘要

The main overall objective of this work is to define the molecular, biological, biochemical and genetic events that control the expression of immunoglobulins. We are working on the control of the expression of antibodies comprising the dominant cross-reactive idiotype associated with the response of A/J mice to the hapten-Rho-azophenylarsonate (Ars). This idiotype is expressed as a family of related antibodies generated by somatic mutation of a few germ-line genes. This proposal deals in depth with the analysis of the timing of somatic mutation induction, i.e. when is it turned on, when, if ever, is it turned off and is mutation alone responsible for the accumulation of high affinity antibodies. We will also study the consequences to the animal of the induction of a large number of mutations altering, at random, induced antibodies. In particular, we will test the idea that mutations can lead to anti-self reactivities. The basic methodology employed is to produce hybridomas from immune animals and then determine their sequence (number of somatic mutations), affinity for antigen and cross-reactivities with DNA and other "self" antigens. We will also test the idea that many "self" antibodies are encoded in the germ-line of the mouse and are modified away from self by somatic mutation. We are also studying the induction of mutation and immunoglobulin secretion in an antigen-specific B cell hybridoma line that is representative of a resting B cell. These studies will provide us with new insights into a fundamental mechanism responsible for the specificity of the humoral immune response. We also expect to learn a great deal about the origins and control of expression of anti-self antibodies in autoimmune disease.

这项工作的主要整体目标是定义分子，控制控制表达的生物学，生化和遗传事件免疫球蛋白。我们正在控制表达的控制抗体包括与 A/J小鼠对Hapten-rho-琼斯烯酸酯（ARS）的反应。这白痴型表示为由相关抗体的家族。一些种系基因的体细胞突变。该提案深入交易通过分析躯体突变诱导的时间，即何时IS 它打开，如果有的话，它关闭并独自突变负责高亲和力抗体的积累。我们也会研究大量诱导动物的后果随机改变突变会诱导抗体。特别是，我们会测试突变会导致反自我激活的想法。所采用的基本方法是从免疫动物中产生杂交然后确定其序列（体突变数），亲和力用于与DNA和其他“自我”抗原的抗原和交叉反应性。我们还将测试许多“自我”抗体编码的想法小鼠的种系，并通过躯体突变远离自我。我们还正在研究突变和免疫球蛋白分泌的诱导在代表A的抗原特异性B细胞杂交瘤系中静止的B细胞。这些研究将为我们提供新的见解负责体液免疫反应特异性的机制。我们还希望学到很多有关起源和控制的知识自身免疫性疾病中抗自身抗体的表达。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

A single germline VH gene segment of normal A/J mice encodes autoantibodies characteristic of systemic lupus erythematosus.

DOI：
10.1084/jem.164.2.614
发表时间：
1986-08-01
期刊：
JOURNAL OF EXPERIMENTAL MEDICINE
影响因子：
15.3
作者：
Naparstek, Y;Andre-Schwartz, J;Manser, T;Wysocki, L J;Breitman, L;Stollar, B D;Gefter, M;Schwartz, R S
通讯作者：
Schwartz, R S

The genetic basis of antibody production: a single heavy chain variable region gene encodes all molecules bearing the dominant anti-arsonate idiotype in the strain A mouse.

抗体产生的遗传基础：单个重链可变区基因编码 A 品系小鼠中具有显性抗胂酸独特型的所有分子。