The Evolution of Lymphocyte Recognition

硬骨鱼具有与高等脊椎动物相似的免疫系统，但似乎不那么复杂。海峡鲶鱼是一种成熟的实验鱼类模型，也是一种重要的商业养殖品种。本实验室此前已分离并定位了通道鲶鱼主抗体（IgM）重链的编码基因，拟开展的研究主要集中在该基因的表达机制上。在这项资助中，他们将研究驱动该基因转录的增强子的性质，以及对该基因表达至关重要的转录因子。在初步实验中，他们已经确定了鲶鱼转录因子与免疫球蛋白基因特征的八聚体基序结合。这个转录因子和它所结合的oct基序似乎经历了共同进化。鲶鱼oct转录因子对与哺乳动物不同序列的基序具有强烈的功能偏好。他们建议通过观察结合亲和力和其他与DNA结合的蛋白质因子来确定这种偏好的基础。转录因子或其他可能的转录因子的作用也将被确定。这些研究不仅将为鲶鱼免疫球蛋白重链基因的调控提供信息，还将为一般免疫球蛋白基因的调控提供信息，并将揭示免疫球蛋白基因在脊椎动物中的表达进化过程。对鱼类免疫系统的研究显示了它们与哺乳动物免疫系统的异同。了解鲶鱼免疫球蛋白基因之间的关系，将为了解免疫球蛋白基因的一般调控提供信息，也将使我们了解免疫球蛋白重链基因在脊椎动物中的表达进化过程。＊＊＊

Abstract 9722996 Warr The bony fish have immune systems which are similar to those of higher vertebrates but seem to be less complex. The channel catfish is a well developed experimental fish model, and also a commercially important aquacultured species. This laboratory has previously isolated and mapped the gene that encodes the heavy chain of the major antibody (IgM) of the channel catfish, and the proposed studies are focused on the mechanisms by which this gene is expressed. In this grant they will investigate the nature of the enhancer that drives transcription of this gene, and the transcription factors that are essential for the expression of the gene. In preliminary experiments they have identified the catfish transcription factor that bind to the "octamer: motif which is characteristic of immunoglobulin genes. This transcription factor and the octomer motif to which it binds appear to have undergone co-evolution. The catfish oct transcription factor has a strong functional preference for a motif that has a different sequence from that found in mammals. They propose to determine the basis for this preference by looking at the binding affinity and other protein factors that bind to DNA. The role of the transcription factor or other possible transcription factors will also be determined. These studies will not only provide information on the regulation of the catfish immunoglobulin heavy chain gene, but will provide information on regulation of immunoglobulin genes in general, and will also indicate how immunoglobulin gene expression has evolved in vertebrates. %%% Studies of the immune system in fish, show similarities and differences from the immune system of mammals. Understanding the relation of the immunoglobulin genes of the catfish, will provide information on the general regulation of immunoglobulin genes, and also will enable us to understand how immunoglublin heavy chain gene expression has evolved in vertebrates. ***