Gastroenterology Research Laboratory, Department of Medicine, University of Iowa College of Medicine, Iowa City, IA, USA.
Immunobiology. 2013 May;218(5):755-61. doi: 10.1016/j.imbio.2012.08.277. Epub 2012 Aug 31.
According to N.K. Jerne the somatic generation of immune recognition occurs in conjunction with germ cell evolution and precedes the formation of the zygote, i.e. operates before clonal selection. We propose that it is based on interspecies inherent, ancestral forces maintaining the lineage. Murine oogenesis may be offered as a model. So in C57BL/10BL sera an anti-A reactive, mercapto-ethanol sensitive glycoprotein of up to now unknown cellular origin, but exhibiting immunoglobulin M character, presents itself "complementary" to a syngeneic epitope, which encoded by histocompatibility gene A or meanwhile accepted ancestor of the ABO gene family, arises predominantly in ovarian tissue and was detected statistically significant exclusively in polar glycolipids. Reports either on loss, pronounced expressions or de novo appearances of A-type structures in various conditions of accelerated growth like germ cell evolution, wound healing, inflammation and tumor proliferation in man and ABO related animals might show the dynamics of ancestral functions guarantying stem cell fidelity in maturation and tissue renewal processes. Procedures vice versa generating pluripotent stem cells for therapeutical reasons may indicate, that any artificially started growth should somehow pass through the germ line from the beginning, where according to growing knowledge exclusively the oocyte's genome provides a completely channeling ancestral information. In predatory animals such as the modern-day sea anemone, ancestral proteins, particularly those of the p53 gene family govern the reproduction processes, and are active up to the current mammalian female germ line. Lectins, providing the dual function of growth promotion and defense in higher plants, are suggested to represent the evolutionary precursors of the mammalian immunoglobulin M molecules, or protein moiety implying the greatest functional diversity in nature. And apart from any established mammalian genetic tree, a common vetch like Vicia cracca, may represent an ancient model of protected reproduction mirroring A-reactive "complementarity" already in a plant. The in its seeds developed, and from the number of chromosomes depending amount of an anti-A(1) specific glycoprotein suggests promotion of germination while simultaneously exerting protection from a soil bacterium, which intriguingly is immobilized by human anti-A immunoglobulin as well. Moreover, in a mammalian ovary the lectin of Dolichos biflorus detects again histo (blood) group A-determining N-acetyl-d-galactosamine epitopes, here signalizing activity of embryonic stem cells. So apparently based on identical, ancestral structures, the dual function of growth promotion and defense, predetermined in a plant genome, might be preserved right up to dominate early mammalian ontogeny.
根据 N.K. Jerne 的观点,免疫识别的体细胞发生伴随着生殖细胞的进化,并先于合子的形成,即发生在克隆选择之前。我们提出,它是基于物种间固有的、维持谱系的祖先力量。鼠类卵母细胞发生可能提供了一个模型。因此,在 C57BL/10BL 血清中,一种抗 A 反应性、巯基乙醇敏感的糖蛋白,到目前为止还不知道其细胞起源,但表现出免疫球蛋白 M 的特征,“互补”于一个同基因表位,该表位由组织相容性基因 A 或 ABO 基因家族的祖先编码,主要在卵巢组织中出现,并在统计上显著仅在极性糖脂中检测到。在人类和 ABO 相关动物的各种加速生长条件下,如生殖细胞进化、创伤愈合、炎症和肿瘤增殖,有关 A 型结构丢失、表达明显或新出现的报告可能显示祖先功能的动态,保证干细胞在成熟和组织更新过程中的保真度。反之,出于治疗原因产生多能干细胞的过程可能表明,任何人为启动的生长都应该从一开始就通过生殖系进行,根据不断增加的知识,只有卵母细胞的基因组提供了完全的祖先信息通道。在现代海葵等捕食动物中,祖先蛋白,特别是 p53 基因家族的蛋白,控制着繁殖过程,并在当前的哺乳动物雌性生殖系中保持活跃。凝集素在高等植物中具有促进生长和防御的双重功能,被认为是哺乳动物免疫球蛋白 M 分子或蛋白质部分的进化前体,在自然界中具有最大的功能多样性。除了任何已建立的哺乳动物遗传树外,一种常见的野豌豆属植物 Vicia cracca 可能代表一种古老的受保护繁殖模式,已经在植物中表现出 A 反应性“互补性”。在其种子中发育的、并且取决于染色体数量的抗 A(1)特异性糖蛋白提示其促进发芽,同时对土壤细菌起到保护作用,而令人好奇的是,这种细菌也被人抗 A 免疫球蛋白固定化。此外,在哺乳动物卵巢中,菜豆属植物的凝集素检测到组织(血液)组 A 决定的 N-乙酰-d-半乳糖胺表位,这里标志着胚胎干细胞的活性。因此,基于相同的、祖先的结构,在植物基因组中预先确定的促进生长和防御的双重功能,可能一直保留到主导早期哺乳动物个体发生。