Immunobiology. 2011 Dec;216(12):1318-21. doi: 10.1016/j.imbio.2011.04.008. Epub 2011 May 27.
The "inappropriate" A-specific ovarian glycosphingolipids discovered in unfertilized C57BL/10J female mice reflect growth processes, which suggest the activity of embryonic stem cells undergoing genetic polymorphism. And the responding anti-GalNAc antibody represents the first classical "natural" antibody, which was unmasked as a highly specific autoantibody. This murine anti-A is subspecifically distinct from the human antibody, discovering by a broader reactivity growth-dependent, xenoreactive A-specific structures also in non-reproductive murine tissues, where an equivalent of the human AB gene family as a cis AB-gene encodes A-and B glycotransferases. Expression of antigen is known to need always more than its encoded enzyme, and the special mechanism which in the C57BL/10J murine ovarian glycospingolipids blocks the expression of "B" still remains still unknown. A herewith arising postulation of a growth-predominating common biological activity may be supported by findings in rats. The number of A-genes here significantly exceeds those of B and in the Wistar rat the A-antigen is only expressed in the wild type, while B-expression requires the transfer of human B. Nevertheless in transgenic rats, the appearance of "A" still remains more pronounced. The observations lead to reports on animals, which do not show AB transferase production or a respective antigen expression in their normal tissues, but inconcistently display A activity in malignant tumors. And respective examples are delivered by phenotype independent neo expressions of "inappropriate" A-specific structures in human cancer. Although in comparison with epitope deletions they are rare, the ubiquitous "natural" (IgM and IgG) anti-A and anti-B levels, against self and not self, irrespective of the blood group in any normal human sera, may reflect invisible "inappropriate" A-specific growth. The role of the associated (auto) anti-B might be different, because B-neo expressions obviously not occur in cancer, and anti-gal-antibodies are supposed to originate primarily from environmental, cross-reactive stimulation, and beyond their functions in defense are otherwise engaged in physiology. In general natural antibody specificities undergo significant phylogenetical changes within the species. However, the in nature wide-spread "natural" anti-A agglutinin specificities survived or even predominated the long-term evolution from the brown trout up to man and still respond to the biological power, i.e. the products of a CAZY glycosyltransferase 6 (ABO) gene family. It is so hypothesized that both, the murine and human "natural" anti-A antibodies represent examples of a still to be analyzed polyclonal response to a provocative, species-independent evolutionary epitope, which arises or escapes by some enzymatic predominance from the genetical polymorphism in a consistent developmental process.
在未受精的 C57BL/10J 雌性小鼠中发现的“不合适”的 A 特异性卵巢糖脂反映了生长过程，提示胚胎干细胞发生遗传多态性的活性。而相应的抗-GalNAc 抗体代表了第一个经典的“天然”抗体，它被揭示为一种高度特异性的自身抗体。这种鼠抗-A 在亚种上与人类抗体不同，通过更广泛的反应性生长依赖性，异种反应性 A 特异性结构也在非生殖性鼠组织中发现，其中人类 AB 基因家族的等效物作为顺式 AB 基因编码 A 和 B 糖基转移酶。已经知道抗原的表达总是需要比其编码酶更多，而在 C57BL/10J 鼠卵巢糖脂中阻止“B”表达的特殊机制仍然未知。因此，一种生长为主导的共同生物学活性的假设可能得到大鼠研究结果的支持。这里 A 基因的数量明显超过 B 基因，而在 Wistar 大鼠中，A 抗原仅在野生型中表达，而 B 表达需要人 B 的转移。然而，在转基因大鼠中，“A”的出现仍然更为明显。这些观察结果导致了关于动物的报告，这些动物在其正常组织中不显示 AB 转移酶的产生或相应抗原的表达，但在恶性肿瘤中表现出 A 活性。相应的例子是由人类癌症中“不合适”的 A 特异性结构的表型独立新表达提供的。尽管与表位缺失相比，它们很少见，但无处不在的“天然”（IgM 和 IgG）抗-A 和抗-B 水平，针对自身和非自身，无论任何正常人类血清中的血型如何，都可能反映出不可见的“不合适”的 A 特异性生长。相关（自身）抗-B 的作用可能不同，因为 B 新表达显然不会在癌症中发生，而抗半乳糖抗体据推测主要来自环境、交叉反应性刺激，除了它们在防御中的功能外，还参与生理学。一般来说，天然抗体特异性在物种内经历了显著的系统发育变化。然而，在自然界中广泛存在的“天然”抗-A 凝集素特异性在从褐鳟鱼到人类的长期进化中幸存下来，甚至占主导地位，并且仍然对生物力量做出反应，即 CAZY 糖苷基转移酶 6（ABO）基因家族的产物。因此，假设鼠和人“天然”抗-A 抗体都是一种仍有待分析的多克隆反应的例子，这种反应是对一种有刺激性的、与物种无关的进化表位的反应，这种表位在一个一致的发育过程中通过某种酶的优势从遗传多态性中产生或逃避。
