Wloch M K, Clarke S H, Gilkeson G S
Department of Medicine, Duke University Medical Center, and Durham Veterans Affairs Hospital, NC 27705, USA.
J Immunol. 1997 Dec 15;159(12):6083-90.
Anti-DNA induced in BALB/c mice by immunization with bacterial (Escherichia coli) DNA resemble spontaneous anti-DNA from lupus mice in V gene use and cross-reactivity with other nuclear Ags, but lack the high V(H) CDR3 arginine content seen in anti-DNA from lupus mice. Moreover, the induced anti-DNA bind bacterial and mammalian single-stranded (ss) DNA and bacterial double-stranded (ds) DNA, but do not bind mammalian dsDNA. This reactivity profile is in contrast to that of the spontaneously arising anti-DNA of lupus mice, among which mammalian dsDNA reactive Abs are prominent. In this study we demonstrate that the addition of arginine to V(H) CDR3 of an induced anti-DNA confers the mammalian dsDNA binding characteristic of anti-DNA from lupus mice. The ability to confer mammalian dsDNA binding is dependent on both the position of the arginine in V(H) CDR3 and the light chain with which the heavy chain is paired, suggesting the light chain plays a more substantial role in DNA binding by this Ab than has previously been reported for other anti-DNA. Our data support the argument that V(H) CDR3 arginines tend to confer antimammalian dsDNA reactivity, leading to censure of B cells expressing these Abs and provides an explanation for the absence of arginine-rich V(H) CDR3 in the bacterial DNA-induced response.
用细菌（大肠杆菌）DNA免疫BALB/c小鼠诱导产生的抗DNA，在V基因使用以及与其他核抗原的交叉反应性方面，类似于狼疮小鼠的自发抗DNA，但缺乏狼疮小鼠抗DNA中所见的高V(H) CDR3精氨酸含量。此外，诱导产生的抗DNA能结合细菌和哺乳动物的单链（ss）DNA以及细菌双链（ds）DNA，但不结合哺乳动物双链DNA。这种反应特性与狼疮小鼠自发产生的抗DNA不同，狼疮小鼠中与哺乳动物双链DNA反应的抗体很突出。在本研究中，我们证明向诱导产生的抗DNA的V(H) CDR3添加精氨酸可赋予狼疮小鼠抗DNA的哺乳动物双链DNA结合特性。赋予哺乳动物双链DNA结合的能力取决于精氨酸在V(H) CDR3中的位置以及与重链配对的轻链，这表明轻链在该抗体与DNA的结合中所起的作用比先前报道的其他抗DNA更为重要。我们的数据支持这样的观点，即V(H) CDR3精氨酸倾向于赋予抗哺乳动物双链DNA反应性，导致表达这些抗体的B细胞受到抑制，并为细菌DNA诱导反应中缺乏富含精氨酸的V(H) CDR3提供了解释。
