Arend Peter
Department of Medicine, Philipps University Marburg/Lahn, Germany; Gastroenterology Research Laboratory, Department of Medicine, University of Iowa College of Medicine, Iowa City, IA, USA; Research Laboratories, Chemie Grünenthal GmbH, D-52062 Aachen, Germany.
Immunobiology. 2016 Jan;221(1):116-27. doi: 10.1016/j.imbio.2015.07.003. Epub 2015 Aug 1.
The formation of a histo (blood) group) ABO phenotype and the exclusion of an autoreactive IgM or isoagglutinin activity arise apparently in identical glycosylation of complementary domains on cell surfaces and plasma proteins. The fundamental O-glycan emptiness of the circulating IgM, which during the neonatal amino acid sequencing of the variable regions is exerting germline-specific O-GalNAc glycan-reactive serine/threonine residues that in the plasma of the adult human blood group O individuals apparently remain associated with the open glycosidic sites on the ABOH convertible red cell surface, must raise suggestions on a transient expression of developmental glycans, which have been "lost" over the course of maturation. In fact, while the mammalian non-somatic, embryogenic stem cell (ESC)- germ cell (GC) transformation is characterized by a transient and genetically as-yet-undefined trans-species-functional O-GalNAc glycan expression, in the C57BL/10 mouse such expression was potentially identified in growth-dependent, blood group A-like GalNAc glycan-bearing, ovarian glycolipids complementary with the syngeneic anti-A reactive IgM, which does not appear in early ovariectomized animals. This non-somatically encoded, polyreactive, ancestral IgM molecule has not undergone clonal selection and does primarily not differentiate between self and non-self and might, due to amino acid hydroxyl groups, highly suggest substrate competition with subsequent O-glycosylations in ongoing ESC-GC transformations and affecting GC maturation. However, the membrane-bound somatic N/O-glycotransferases, which initiate, after formation of the zygote, the complex construction of the human ABO phenotypes in the trans cisternae of the Golgi apparatus, are associated and/or completed with soluble enzyme versions exerting identical specificities in plasma and likely competing vice versa by glycosylation of neonatal IgM amino acids, where they suggest to accomplish the clearance of anti-A autoreactivity at germline serine and threonine residues. Sustaining the lineage-maintaining position of the classic A allele and the discovery of the OA hybrid alleles at the normal ABO locus and in heterozygous ESC lines have, together with clinical observations, raised discussions about a silent A-allelic support within blood group O reproduction. However, the question of whether a fictional "continued blood group O inbreeding" ultimately occurs without the A-allelic or somatic function remains unanswered because the genetic relationship between non-somatic O-GalNAc-glycosylations that operate before sperm-egg recognition and somatic O-GalNAc-glycosylations that arise after the formation of the zygote remains to be elucidated.
组织（血型）ABO表型的形成以及自身反应性IgM或同种凝集素活性的排除，显然源于细胞表面和血浆蛋白互补结构域相同的糖基化。循环IgM基本的O-聚糖空缺，在可变区的新生儿氨基酸测序过程中，其发挥种系特异性的O-GalNAc聚糖反应性丝氨酸/苏氨酸残基，在成年人类O型血个体的血浆中，这些残基显然仍与ABOH可转换红细胞表面的开放糖苷位点相关，这必然引发了关于发育聚糖短暂表达的推测，这些聚糖在成熟过程中已经“丢失”。事实上，虽然哺乳动物的非体细胞、胚胎干细胞（ESC）向生殖细胞（GC）的转化以短暂且基因上尚未明确的跨物种功能性O-GalNAc聚糖表达为特征，但在C57BL/10小鼠中，这种表达可能在生长依赖性、血型A样含GalNAc聚糖的卵巢糖脂中被识别，这些糖脂与同基因抗A反应性IgM互补，而在早期去卵巢动物中未出现。这种非体细胞编码的、多反应性的、祖先IgM分子未经历克隆选择，主要不区分自我和非自我，并且由于氨基酸羟基，很可能在正在进行的ESC-GC转化中与随后的O-糖基化存在底物竞争，从而影响GC成熟。然而，膜结合的体细胞N/O-糖基转移酶在合子形成后，在高尔基体的反式潴泡中启动人类ABO表型的复杂构建，它们与在血浆中发挥相同特异性的可溶性酶版本相关联和/或完成，并且可能通过新生儿IgM氨基酸的糖基化反之竞争，在那里它们表明要在种系丝氨酸和苏氨酸残基处完成抗A自身反应性的清除。维持经典A等位基因的谱系维持地位以及在正常ABO位点和杂合ESC系中发现OA杂交等位基因，连同临床观察结果，引发了关于O型血繁殖中沉默A等位基因支持的讨论。然而，虚构的“持续的O型血近亲繁殖”在没有A等位基因或体细胞功能的情况下最终是否会发生这个问题仍然没有答案，因为在精卵识别之前起作用的非体细胞O-GalNAc糖基化与合子形成后出现的体细胞O-GalNAc糖基化之间的遗传关系仍有待阐明。
