Havele C, Wegmann T G, Longenecker B M
J Exp Med. 1982 Aug 1;156(2):321-36. doi: 10.1084/jem.156.2.321.
Hematopoietic chimeras were produced at four different stages of ontogeny between two allogeneic strains of chickens. All chimeras produced by parabiosis at day 12 of embryogenesis and the majority (83%) of the ones produced at day 15 by intravenous injection of allogeneic stem cells remained healthy, chimeric, and specifically tolerant at both the humoral and cell-mediated level throughout a long examination period. Chimeras generated at day 17 of embryogenesis demonstrated specific unresponsiveness at the cell-mediated level but produced specific anti-donor alloantibodies directed against erythrocyte-associated major histocompatibility complex (MHC) (B-G) antigens. These chimeras and a minority (17%) of the chimeras generated at day 15 of embryogenesis developed severe antibody-mediated autoimmune hemolytic anemia after the 5th mo of age and succumbed to massive bursal lymphomas and metastases by the 10th mo of age. The immunological and pathological characteristics of these birds appear to reflect an autoimmune state rather than one of tolerance. Erythroid chimeras generated at day 21 of ontogenic development displayed normal levels of GVH reactivity. These birds were eventually able to eliminate the chimeric state and remained healthy until deliberately killed. These results show that there is a critical period in embryogenesis during which the induction of allogeneic erythrocytic chimerism leads to the development, in adult life, of severe autoimmune anemia, B cell lymphomas, and death. B-G MHC antigens are erythroid differentiation antigens of the chicken. Polymorphic determinants on B-G antigens appear to be important cross-reactive determinants (with environmental bacteria), against which a high background immunity exists. Evidence is presented that the immune response to B-G antigens is responsible for the development of autoimmunity and other pathological events that follow and that tolerance to class I MHC antigens (B-F antigens) shared by lymphocytes erythrocytes is maintained at the same time that B-G tolerance is broken.
在两种异基因鸡品系之间的个体发育的四个不同阶段产生了造血嵌合体。在胚胎发育第12天通过联体共生产生的所有嵌合体，以及在第15天通过静脉注射异基因干细胞产生的大多数（83%）嵌合体，在整个较长的检查期内都保持健康、嵌合状态，并且在体液和细胞介导水平上具有特异性耐受性。在胚胎发育第17天产生的嵌合体在细胞介导水平上表现出特异性无反应性，但产生了针对红细胞相关主要组织相容性复合体（MHC）（B-G）抗原的特异性抗供体同种抗体。这些嵌合体以及在胚胎发育第15天产生的少数（17%）嵌合体在5月龄后发生了严重的抗体介导的自身免疫性溶血性贫血，并在10月龄时死于大量法氏囊淋巴瘤和转移瘤。这些鸡的免疫和病理特征似乎反映的是一种自身免疫状态而非耐受状态。在个体发育第21天产生的红系嵌合体表现出正常水平的移植物抗宿主反应性。这些鸡最终能够消除嵌合状态并保持健康，直到被故意处死。这些结果表明，在胚胎发育过程中存在一个关键时期，在此期间诱导异基因红系嵌合会导致成年后发生严重的自身免疫性贫血、B细胞淋巴瘤并死亡。B-G MHC抗原是鸡的红系分化抗原。B-G抗原上的多态性决定簇似乎是重要的交叉反应决定簇（与环境细菌），针对这些决定簇存在较高的背景免疫。有证据表明，对B-G抗原的免疫反应是自身免疫以及随后发生的其他病理事件的原因，并且在打破B-G耐受性的同时，淋巴细胞和红细胞共有的I类MHC抗原（B-F抗原）的耐受性得以维持。
