MOLECULAR BASIS OF IMMUNOGLOBULIN HEAVY CHAIN SWITCH

类别转换的过程，即B细胞从产生 一类免疫球蛋白（IG）与另一类免疫球蛋白的相互作用受到高度调节， 不同的类别响应于不同的抗原而表达， 身体的不同部位。IG类转换是由DNA 重组事件，其将Cmu基因替换为其它基因之一， 重链恒定区（CH）基因位于Cmu基因的3'。如何 该事件的特异性受控是未知的。但却 已经证明IgM+细胞能够转换为特异性抗体， 类具有相应的未重排的CH基因在一个可接近的或 活跃的染色质状态，正如这些具体的事实所证明的那样， CH基因是低甲基化的并且是转录活性的。 我们建议继续研究对IG类的规管 使用小鼠B细胞淋巴瘤进行转换，I. 29 IgM+细胞克隆自 这种淋巴瘤可以被诱导从IgM的表达转变为伊加，或者 通过用LPS治疗，IgE或IgG2a的频率较低。该细胞系 将被用来询问关于类特异性如何 控制，特别是注重从转录的作用， 在重链转换之前的种系IG C α基因。我们计划 确定某些调节转换的T细胞淋巴因子 激活生殖系α和β基因的转录。我们也 我建议开始鉴定在B细胞中诱导的基因的cDNA 在进行阶级转换的过程中。我们将尝试选择 可以在转染的质粒中引起开关重组的cDNA。

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.