MECHANISM OF IMMUNOGLOBULIN HYPERMUTATION

本申请是一项新的资助，研究免疫球蛋白（IG）基因体细胞超突变的机制。我们以前的工作表明，这一过程取决于转录的启动。新的目标是确定转录与体细胞突变过程的关系，作为突变靶点的一级序列的作用以及顺式作用调控元件的组成。最后，我们计划克隆和鉴定编码假定增变因子的基因。这些研究对于理解lg库的产生具有对抗任何外来抗原（包括肿瘤抗原）的潜力是很重要的。此外，体细胞超变也与自身免疫有关。最后，lg基因体细胞突变过程中会产生某些恶性淋巴肿瘤，了解其机制将有助于阐明肿瘤的发生，并有希望，其预防。

This application is for a new grant to study the mechanism of somatic hypermutation of immunoglobulin (Ig) genes. Our previous work has shown that this process depends on initiation of transcription. The new aims are directed at determining how transcription relates to the somatic mutation process, what the role is of the primary sequence which is the target for mutation and what the cis-acting regulatory elements consist of. Finally, we plan to clone and identify the gene(s) that encode a postulated mutator factor. These studies are important to understand the creation of the lg repertoire with the potential of reacting against any foreign antigen, including tumor antigens. Also, somatic hypermutation has been implicated in autoimmunities. Finally, certain malignant lymphoid tumors arise during the lg gene somatic mutation process and understanding its mechanism will shed light on the tumorigenesis and, hopefully, its prevention.