Spitzer R E, Stitzel A E, Tsokos G C
Department of Pediatrics, State University of New York Health Science Center, Syracuse 13210.
J Pediatr. 1990 May;116(5):S103-8. doi: 10.1016/s0022-3476(05)82711-8.
The origin of autoantibody production was studied with the use of antibody to the alternative pathway C3 convertase (C3 nephritic factor (C3NeF), as a model. Pokeweed mitogen stimulation of peripheral mononuclear cells from newborn infants, normal adults, and patients with membranoproliferative glomerulonephritis indicated that the ability to make C3NeF is apparently present in everyone from the time of birth. In addition, C3NeF appeared to express a single or very limited idiotope (21/21 isolates). The data also suggest that the elaboration of C3NeF may approximate an antibody response after immunization. Thus the C3NeF fraction of the total IgG or IgM produced in culture by pokeweed mitogen-stimulated mononuclear cells from normal neonates and adults, as well as from patients, was in the range of the production of specific antibody. Further, both IgG and IgM C3NeF produced by cells from these normal individuals, including newborn infants, had an affinity for antigen (10(8) to 10(9) L/mol) that was also in the range of specific antibody. Most of the autoantibody molecules (5/7) from serum were IgG3; two B cell clones producing C3NeF were CD5-negative. These experiments indicate that unmutated germline genes are used in the production of C3NeF and that a limited spectrum of antiidiotypic antibodies regulate its production.
以针对替代途径C3转化酶的抗体(C3肾炎因子(C3NeF))作为模型,研究了自身抗体产生的起源。用美洲商陆丝裂原刺激新生儿、正常成年人以及膜增生性肾小球肾炎患者的外周单核细胞,结果表明,从出生时起,每个人显然都具备产生C3NeF的能力。此外,C3NeF似乎表达单一或非常有限的独特型(21个分离株中有21个)。数据还表明,C3NeF的产生可能类似于免疫后的抗体反应。因此,美洲商陆丝裂原刺激的正常新生儿、成年人以及患者的单核细胞在培养物中产生的总IgG或IgM中的C3NeF部分,处于特异性抗体产生的范围内。此外,包括新生儿在内的这些正常个体的细胞产生的IgG和IgM C3NeF对抗原都具有亲和力(10⁸至10⁹L/mol),这也在特异性抗体的范围内。血清中的大多数自身抗体分子(7个中有5个)为IgG3;产生C3NeF的两个B细胞克隆为CD5阴性。这些实验表明,未突变的种系基因用于C3NeF的产生,并且有限谱的抗独特型抗体调节其产生。