Gilkeson G S, Bloom D D, Pisetsky D S, Clarke S H
Medical Research Service, Durham VA Medical Center, Durham, NC 27705.
J Immunol. 1993 Aug 1;151(3):1353-64.
Immunization of normal mice with bacterial DNA induces a significant anti-DNA response that includes antibodies resembling some lupus anti-DNA in their binding properties, although lacking specificity for mammalian dsDNA. To determine the structure of these induced antibodies and their relationship to anti-DNA from lupus mice, we have characterized the clonality and selected V-region sequences of a panel of 20 anti-DNA antibodies from 3 BALB/c mice immunized with ssDNA from Escherichia coli. Southern blot analysis of H and L chain rearrangements indicated that two of the animals expressed pairs of clonally related antibodies. Amino acid sequences of 10 of the induced antibodies demonstrated predominant utilization of J558 family VH genes and JH4 in association with various DH, J kappa and V kappa genes. Among the VH CDR3 of these 10 antibodies, 4 displayed arginine residues as a result of N region additions. None of these antibodies, however, had more than one arginine residue in VH CDR3 nor arginines at positions 100 or 100a, characteristic features of lupus antibodies to dsDNA. These results suggest that normal mice immunized with bacterial DNA display certain facets of DNA Ag drive, although lacking the mechanisms for the production of antibodies to mammalian dsDNA.
用细菌DNA免疫正常小鼠可诱导显著的抗DNA反应,该反应包括一些在结合特性上类似于某些狼疮抗DNA的抗体,尽管对哺乳动物双链DNA缺乏特异性。为了确定这些诱导抗体的结构及其与狼疮小鼠抗DNA抗体的关系,我们对3只经大肠杆菌单链DNA免疫的BALB/c小鼠的一组20种抗DNA抗体的克隆性和选定的V区序列进行了表征。对重链和轻链重排的Southern印迹分析表明,其中两只动物表达了成对的克隆相关抗体。10种诱导抗体的氨基酸序列显示,J558家族VH基因和JH4与各种DH、Jκ和Vκ基因相关联的使用占主导地位。在这10种抗体的VH CDR3中,4种由于N区添加而显示精氨酸残基。然而,这些抗体中没有一种在VH CDR3中有超过一个精氨酸残基,也没有在100或100a位有精氨酸,而这些是狼疮双链DNA抗体的特征。这些结果表明,用细菌DNA免疫的正常小鼠表现出DNA抗原驱动的某些方面,尽管缺乏产生针对哺乳动物双链DNA抗体的机制。