Bloom D D, St Clair E W, Pisetsky D S, Clarke S H
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599.
Eur J Immunol. 1994 Jun;24(6):1332-8. doi: 10.1002/eji.1830240614.
Autoantibodies to ribonucleoproteins (RNP) occur prominently in human systemic lupus erythematosus and murine lupus models. In previous studies we demonstrated a relationship in MRL/Mp-lpr/lpr (MRL/lpr) mice between antibodies to Sm, an RNP autoantigen, and antibodies to DNA. Thus, many anti-Sm monoclonals bound DNA and expressed the same V region genes as anti-DNA. In addition, many had multiple VHCDR3 Arg residues suggestive of selection by DNA, and some had somatic mutations suggesting selection for mutant B cells by DNA. To determine whether autoantibodies to other RNP antigens are also associated with the anti-DNA response, we have analyzed the response to the La RNP. Six anti-La B cell hybridomas were generated from a single MRL/lpr mouse. Southern blot analysis of Ig V gene rearrangements and V gene sequences indicated two clonally related pairs, suggesting an oligoclonal response. Antibodies from all six hybridomas bound single-stranded DNA, while antibodies from five hybridomas bound double-stranded DNA. Two hybridomas expressed a VH7183 gene which is used by members of two previously reported anti-DNA clones and two anti-Sm/DNA clones of MRL/lpr origin. These data demonstrate an association between the anti-La and anti-DNA responses in MRL/lpr mice, suggesting that cross-reactive anti-RNP and anti-DNA responses are a general feature of autoimmunity in this lupus model.
核糖核蛋白（RNP）自身抗体在人类系统性红斑狼疮和小鼠狼疮模型中显著存在。在先前的研究中，我们在MRL/Mp-lpr/lpr（MRL/lpr）小鼠中证明了针对RNP自身抗原Sm的抗体与针对DNA的抗体之间存在关联。因此，许多抗Sm单克隆抗体结合DNA，并表达与抗DNA相同的V区基因。此外，许多抗体具有多个VHCDR3精氨酸残基，提示由DNA进行选择，并且一些抗体具有体细胞突变，提示由DNA对突变B细胞进行选择。为了确定针对其他RNP抗原的自身抗体是否也与抗DNA反应相关，我们分析了对La RNP的反应。从一只MRL/lpr小鼠中产生了六个抗La B细胞杂交瘤。对Ig V基因重排和V基因序列的Southern印迹分析表明存在两对克隆相关的杂交瘤，提示为寡克隆反应。所有六个杂交瘤的抗体均结合单链DNA，而五个杂交瘤的抗体结合双链DNA。两个杂交瘤表达VH7183基因，先前报道的两个抗DNA克隆以及源自MRL/lpr的两个抗Sm/DNA克隆的成员也使用该基因。这些数据证明了MRL/lpr小鼠中抗La反应与抗DNA反应之间存在关联，提示交叉反应性抗RNP和抗DNA反应是该狼疮模型自身免疫的一个普遍特征。
