Warrington R J, Wong S K, Ramdahin S, Rutherford W J
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Scand J Immunol. 1995 Oct;42(4):397-406. doi: 10.1111/j.1365-3083.1995.tb03673.x.
It is possible to identify, in Epstein-Barr virus-transformed normal human cord blood B cell populations, cells present at a low frequency that produce IgG antibodies specific for dsDNA. By cloning out these B cells as immortalized monoclonal cell lines, it could be shown that the antibodies were the products of CD5 positive B cells. Two monoclonal anti-dsDNA antibodies were derived from cell lines T52 and A7 and these were further characterized as anionic (pI approximately 6.4) IgG4 kappa antibodies that bound with affinities of 7.18 x 10(9) l/mol and 3.28 x 10(9) l/mol, respectively, to dsDNA but did not bind to ssDNA. These affinities were similar to those of polyclonal IgG anti-dsDNA antibodies from lupus patients, which ranged from 1 x 10(9) -8.9 x 10(10) l/mol. Both T52 and A7 monoclonal anti-dsDNA antibodies were recognized by cord blood-derived IgM antibodies. These IgM antibodies were not rheumatoid factors but bound to the F(ab')2 of A7 and T52 while failing to recognize T50, which is an autologous IgG4 kappa monoclonal antibody without specificity for dsDNA. A cloned B cell line A24 generated from the same cord blood sample as A7 produced an IgM monoclonal antibody that bound to the heavy chains of T52 and A7, but not T50 on Western blot and inhibited the binding of these antibodies to dsDNA. A7 and T52 competitively inhibited each other in their binding to the anti-idiotype A24, and A24 inhibited the binding to dsDNA of some polyclonal IgG anti-dsDNA antibodies purified from sera of lupus patients. The level of inhibition of binding of these antibodies to dsDNA was directly proportional to the levels of expression of the idiotype recognized by A24 on these antibodies. The normal human cord blood, therefore, may contain cells that form an idiotype/anti-idiotype network in which the idiotype is expressed on IgG antibodies with specificity for dsDNA and the anti-idiotype is an IgM antibody that binds to a heavy chain idiotope in such a way as to interfere with its interaction with dsDNA. The presence of a similar idiotype on some polyclonal anti-dsDNA antibodies in lupus that are similarly inhibitable by the cord blood-derived anti-idiotype raises the possibility that this network may persist in later life and perhaps become dysfunctional in systemic lupus erythematosus.
在爱泼斯坦 - 巴尔病毒转化的正常人脐血B细胞群体中，有可能识别出低频存在的、产生对双链DNA具有特异性的IgG抗体的细胞。通过将这些B细胞克隆为永生化单克隆细胞系，可以证明这些抗体是CD5阳性B细胞的产物。从细胞系T52和A7获得了两种单克隆抗双链DNA抗体，它们进一步被鉴定为阴离子型（pI约为6.4）IgG4 κ抗体，分别以7.18×10⁹ l/mol和3.28×10⁹ l/mol的亲和力与双链DNA结合，但不与单链DNA结合。这些亲和力与狼疮患者的多克隆IgG抗双链DNA抗体相似，后者的亲和力范围为1×10⁹ - 8.9×10¹⁰ l/mol。脐血来源的IgM抗体可识别T52和A7单克隆抗双链DNA抗体。这些IgM抗体不是类风湿因子，但能与A7和T52的F(ab')₂结合，而不能识别T50，T50是一种对双链DNA无特异性的自体IgG4 κ单克隆抗体。从与A7相同的脐血样本中产生的克隆B细胞系A24产生了一种IgM单克隆抗体，该抗体在蛋白质印迹上与T52和A7的重链结合，但不与T50结合，并抑制这些抗体与双链DNA的结合。A7和T52在与抗独特型A24的结合中相互竞争抑制，并且A24抑制从狼疮患者血清中纯化的一些多克隆IgG抗双链DNA抗体与双链DNA的结合。这些抗体与双链DNA结合的抑制水平与A24识别的独特型在这些抗体上的表达水平直接相关。因此，正常人脐血可能含有形成独特型/抗独特型网络的细胞，其中独特型在对双链DNA具有特异性的IgG抗体上表达，而抗独特型是一种IgM抗体，它以干扰其与双链DNA相互作用的方式与重链独特位结合。狼疮患者一些多克隆抗双链DNA抗体上存在类似的独特型，且同样可被脐血来源的抗独特型抑制，这增加了这种网络可能在以后的生活中持续存在并可能在系统性红斑狼疮中功能失调的可能性。
