MOLECULAR BASIS OF IMMUNOGLOBULIN HEAVY CHAIN SWITCH

免疫球蛋白重链开关的分子基础

• 批准号: 3135190
• 负责人: Janet M. Stavnezer
• 金额: $ 31.59万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-08-01 至 1994-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3135190
• 关键词: B lymphocyte; DNA replication; RNA biosynthesis; T lymphocyte; complementary DNA; endoribonucleases; gene complementation; gene expression; genetic mapping; immunofluorescence technique; immunogenetics; immunoglobulin A; immunoglobulin genes; immunoglobulin isotypes; immunoglobulin structure; immunoglobulins; immunoregulation; interleukin 4; laboratory mouse; lymphoma; messenger RNA; molecular cloning; molecular oncology; neoplastic cell culture for noncancer research; nucleic acid sequence; plasmids; proteins; tissue /cell culture; transfection; transposon /insertion element

The process of class switching, whereby B cells switch from production of one class of immunoglobulin (Ig) to another, is highly regulated as different classes are expressed in response to different antigens and at different sites in the body. Ig class switching is effected by a DNA recombination event which replaces the Cmu gene with one of the other heavy chain constant region (CH) genes located 3' to the Cmu gene. How the specificity of this event is controlled is unknown. However, it has been shown that IgM+ cells capable of switching to specific antibody classes have the corresponding unrearranged CH genes in an accessible or active chromatic state, as demonstrated by the fact that these specific CH genes are hypomethylated and are transcriptionally active. We propose to continue our studies on the regulation of Ig class switching using the mouse B cell lymphoma, I.29 IgM+ cells cloned from this lymphoma can be induced to switch from expression of IgM to IgA or less frequently to IgE or IgG2a, by treatment with LPS. This cell line will be used to ask questions about how the class specificity is controlled, especially focusing on the unction of transcription from the germline Ig C alpha genes prior to heavy chain switching. We plan to determine how certain T cell lymphokines which regulate switching activate transcription of the germline alpha and epsilon genes. We also propose to begin to identify cDNAs for genes which are induced in B cells in the process of undergoing class switching. We will attempt to select cDNAs that can cause switch recombination in a transfected plasmid.

类切换的过程，从而从生产中切换了B细胞 一类免疫球蛋白（IG）对另一种免疫球蛋白（IG）被高度调节为 响应不同的抗原和AT表示不同类别的类别 体内不同的位置。 IG类切换由DNA实现 重组事件将CMU基因替换为另一个 重链常数区域（CH）基因位于CMU基因3'。如何 该事件的特异性是未知的。但是，它有 已显示能够切换到特定抗体的IgM+细胞 课程在可访问或 主动色状态，如这些特定的事实所证明 CH基因是甲基化的，并且具有转录活性。 我们建议继续对IG类调节的研究 使用小鼠B细胞淋巴瘤切换，i.29 IgM+细胞从 该淋巴瘤可被诱导从IgM的表达转换为IgA或 通过使用LPS处理，不太频繁地使用IgE或IgG2a。该单元线 将用于询问有关课堂特异性的问题 受控，特别是关注从 重链转换之前的生殖线Ig Cα基因。我们计划 确定如何调节开关的某些T细胞淋巴动物 激活种系α和Epsilon基因的转录。我们也是 建议开始鉴定在B细胞中诱导的基因的cDNA 在进行课程切换的过程中。我们将尝试选择 可以在转染的质粒中导致开关重组的cDNA。