Department of Microbiology and Immunology.
Integr Comp Biol. 2003 Apr;43(2):347-59. doi: 10.1093/icb/43.2.347.
Although the capacity of cells to respond to environmental challenges such as oxidative damage are ancient evolutionary developments that have been carried through to modern higher vertebrates as "innate" immunity, the characteristic immune response of vertebrates is a relatively recent evolutionary development that is present only in jawed vertebrates. The vertebrate "combinatorial" response is defined by the presence of lymphocytes as specific antigen recognition cells and by the complete panel of antibodies, T cell receptors, and major histocompatibility complex molecules all of which are members of the immunoglobulin family. Its emergence in evolution was an extremely rapid event (approximately 10 million years) that was catalyzed by the horizontal transfer of recombinase activator genes (RAG) from microbes to an ancestral jawed vertebrate. RAGs occur in jawed vertebrates, but have not been found in invertebrates and other intermediate species. We propose that antigen recognition capacity contributed by this novel combinatorial mechanism gave jawed vertebrates the ability to recognize the entire range of potential antigenic molecular structures, including self components and molecules of infectious microbes not shared with vertebrates. The contrast within the vertebrates is striking because the most ancient extant jawed vertebrates, sharks and their kin, have the complete panoply of T-cell receptors, antibodies, MHC products and RAG genes, whereas agnathans possess cells resembling lymphocytes but ostensibly lack all of the molecules definitive of combinatorial immunity. Another vertebrate innovation may have been the utilization of nuclear receptor superfamily, in the regulation of lymphocytes and other cells of the immune lineage. Unlike, RAG, however, this superfamily occurs in all metazoans with the exception of sponges.
虽然细胞应对环境挑战（如氧化损伤）的能力是一种古老的进化发展，一直延续到现代高等脊椎动物的“先天”免疫中，但脊椎动物的特征免疫反应是一种相对较新的进化发展，仅存在于有颌脊椎动物中。脊椎动物的“组合”反应的定义是存在淋巴细胞作为特定抗原识别细胞，以及完整的抗体、T 细胞受体和主要组织相容性复合体分子面板，所有这些都是免疫球蛋白家族的成员。它在进化中的出现是一个极其迅速的事件（大约 1000 万年），是由重组激活基因（RAG）从微生物到祖先有颌脊椎动物的水平转移所催化的。RAG 存在于有颌脊椎动物中，但在无脊椎动物和其他中间物种中未发现。我们提出，这种新的组合机制提供的抗原识别能力使有颌脊椎动物能够识别潜在抗原分子结构的整个范围，包括自身成分和与脊椎动物不同的传染性微生物分子。脊椎动物内部的对比非常明显，因为最古老的现存有颌脊椎动物鲨鱼及其近亲拥有完整的 T 细胞受体、抗体、MHC 产物和 RAG 基因，而无颌类动物拥有类似于淋巴细胞的细胞，但显然缺乏组合免疫的所有定义分子。另一个脊椎动物的创新可能是利用核受体超家族来调节淋巴细胞和免疫谱系的其他细胞。然而，与 RAG 不同的是，这个超家族存在于除海绵动物以外的所有后生动物中。
