Mitamura K, Suenaga R, Wilson K B, Abdou N I
Immunology Research Laboratory, St. Luke's Hospital, University of Missouri-Kansas City 64111, USA.
Clin Immunol Immunopathol. 1996 Feb;78(2):152-60. doi: 10.1006/clin.1996.0024.
V gene sequences encoding two lupus-derived human monoclonal IgMk anti-ssDNA antibodies (2F7 and 1A6) and CD5 mRNA expression by the corresponding hybridomas were investigated. Both antibodies displayed V gene sequences nearly in germline configuration compared with their putative germline counterparts. It appeared that 2F7 used hv3019b9/HUD-3/JH6 and 12La/Jk2, while 1A6 utilized HHG19/D31-HUD-3/JH2 and Humkv328h5/Jk1. Assessment of R/S mutation ratios suggested that 2F7 and 1A6 have not undergone the antigen-driven somatic mutation. The HCDR3 featuring arginine appeared to be important in determining the anti-ssDNA specificity. CD5 mRNA was negative in both hybridomas. Since 2F7 was previously shown to be monospecific and of high affinity, these results provide the molecular basis of such unique immunochemical characteristics of the IgM anti-ssDNA antibody. Germline V genes and N sequences may be selected to confer such anti-ssDNA specificity during V gene rearrangement, which might involve CD5-negative B cells.
对编码两种狼疮来源的人单克隆IgMκ抗单链DNA抗体(2F7和1A6)的V基因序列以及相应杂交瘤的CD5 mRNA表达进行了研究。与推测的种系对应序列相比,两种抗体的V基因序列几乎呈种系构型。似乎2F7使用hv3019b9/HUD - 3/JH6和12La/Jk2,而1A6利用HHG19/D31 - HUD - 3/JH2和Humkv328h5/Jk1。R/S突变率评估表明,2F7和1A6未经历抗原驱动的体细胞突变。具有精氨酸的重链互补决定区3(HCDR3)似乎在确定抗单链DNA特异性方面很重要。两种杂交瘤中的CD5 mRNA均为阴性。由于2F7先前已显示为单特异性且具有高亲和力,这些结果为IgM抗单链DNA抗体这种独特免疫化学特性提供了分子基础。在V基因重排过程中,可能会选择种系V基因和N序列来赋予这种抗单链DNA特异性,这可能涉及CD5阴性B细胞。