SIGNALS FOR L CHAIN REARRANGEMENT BY A CHIMERIC H CHAIN

嵌合 H 链重排 L 链的信号

• 批准号: 2806558
• 负责人: ROBERTA R POLLOCK
• 金额: $ 9.14万
• 依托单位: OCCIDENTAL COLLEGE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2806558
• 关键词: B lymphocyte; biological signal transduction; cell differentiation; chimeric proteins; flow cytometry; gene rearrangement; genetically modified animals; immunoglobulin genes; immunoglobulins; laboratory mouse

DESCRIPTION (Adapted from the Investigator's Abstract): The immunoglobulin heavy chain loci initiates gene rearrangements at the late pro-B cell stage of development. The first rearrangement involves the selection of a D and J segment for recombination. This is followed by the selection of a V segment. If these recombinations are successful the developing B cell synthesizes the heavy chain which is expressed on the membrane in association with the surrogate light chain (the pre-B cell receptor). It is currently thought that signaling through the pre-B cell receptor stops any further rearrangement of the other heavy chain allele and initiates light chain rearrangement. This competitive renewal will continue to study the molecular mechanisms responsible for allelic exclusion and initiation of light chain rearrangements using a transgenic mouse line developed during the previous funding period. The transgenic line expresses a murine VDJ expressed with a human gamma 1 constant region. The interesting feature of this line is that B-2 cells from young mice display allelic exclusion without initiating light chain rearrangements. This suggests that these two processes might be independently regulated. The present application will use this transgenic line in experiments designed to uncover the way that the pre-B cell receptor regulates light chain rearrangements.

描述（根据研究者的摘要改编）：免疫球蛋白重链基因座在发育的晚期细胞阶段启动基因重排。第一个重排涉及选择D和J段进行重组。接下来是选择V段。如果这些重组成功，则发育中的B细胞合成了与替代轻链（PER-B细胞受体）相关的膜上表达的重链。目前，人们认为，通过前B细胞受体的信号传导会停止其他重型链等位基因的任何进一步重排，并启动轻链重排。这种有竞争力的更新将继续研究负责在上一个融资期间开发的转基因小鼠线来使等位基因排除和启动轻链重排的分子机制。转基因线表示用人伽玛1常数区域表达的鼠VDJ。该线路的有趣特征是，来自年轻小鼠的B-2细胞在不引发轻链重排的情况下显示等位基因排除。这表明这两个过程可能会受到独立的监管。本应用将在实验中使用此转基因线，以揭示前B细胞受体调节轻链重排的方式。