Ohga S, Yoshikai Y, Kishihara K, Matsuzaki G, Ogimoto M, Nomoto K
Department of Immunology, Kyushu University, Fukuoka, Japan.
Immunology. 1990 Jun;70(2):216-22.
In order to search for a possible role of abnormally proliferating T cells in developing autoimmune disease in lpr mice, and to define the difference of the T cells among various lpr-congeneic mice with different clinicopathological findings, the T-cell receptor (TcR) V beta gene expression in the enlarged lymph nodes (LN) of C3H/HeJ-lpr/lpr (C3H-lpr), C57BL/6-lpr/lpr (B6-lpr) and MRL/Mp-lpr/lpr (MRL-lpr) mice was analysed. A RNA blot analysis using several V beta-specific probes showed that the V beta 3 gene, whose products are important for recognizing Mlsb/a, was used in B6-lpr and MRL-lpr with the Mlsb/b but not in C3H-lpr with the Mlsb/a. The V beta 5 gene, which is selectively related to I-E molecules, was predominantly used in B6-lpr(I-E-) but not in C3H-lpr(I-E+) nor MRL-lpr(I-E+). Similarly, the V12 gene was also expressed in B6-lpr but not in C3H-lpr. To compare in detail in V beta repertoire among lpr mice with different major histocompatibility complex (MHC) backgrounds, the V beta gene sequences in the cDNA libraries from LN cells of C3H-lpr were analysed, following the recent investigation of B6-lpr mice (Ohga et al., 1989). Eleven beta-chain cDNA out of 32 beta cDNA in B6-lpr and 24 beta-chain cDNA out of 55 beta cDNA in C3H-lpr were found to contain sequences with open reading frames that potentially encode functional TcR beta-chain. The frequencies of the messages in the cDNA libraries from these mice were consistent with the RNA blot analysis using V beta 3- and V beta 5-specific probes. It was notable that 36% of the functional beta-chain mRNA in B6-lpr and 50% of the beta mRNA in C3H-lpr expressed the V beta 8 gene family. When the TcR V beta gene expression was compared between the LN cells in C3H-lpr, B6-lpr and MRL-lpr, as reported by Singer et al. (1986), the usage of V beta genes other than the V beta 8 gene family in B6-lpr (H-2b) LN cells differed significantly from those in C3H-lpr (H-2k) and MRL-lpr (H-2k). The results presented here indicate that the usage of V beta genes is heavily influenced by the genetic background of lpr mice, similar to normal mice, but with preferential usage of the V beta 8 gene family as a common structural feature in lpr gene-induced cell populations.
为了探寻异常增殖的T细胞在lpr小鼠自身免疫性疾病发生过程中可能发挥的作用，并明确具有不同临床病理表现的各种lpr同基因小鼠之间T细胞的差异，我们分析了C3H/HeJ-lpr/lpr（C3H-lpr）、C57BL/6-lpr/lpr（B6-lpr）和MRL/Mp-lpr/lpr（MRL-lpr）小鼠肿大淋巴结（LN）中T细胞受体（TcR）Vβ基因的表达情况。使用几种Vβ特异性探针进行的RNA印迹分析表明，其产物对识别Mlsb/a很重要的Vβ3基因，在具有Mlsb/b的B6-lpr和MRL-lpr中被使用，但在具有Mlsb/a的C3H-lpr中未被使用。与I-E分子选择性相关的Vβ5基因，主要在B6-lpr（I-E-）中被使用，而在C3H-lpr（I-E+）和MRL-lpr（I-E+）中未被使用。同样，V12基因也在B6-lpr中表达，但在C3H-lpr中未表达。为了更详细地比较具有不同主要组织相容性复合体（MHC）背景的lpr小鼠之间的Vβ谱系，在对B6-lpr小鼠进行近期研究（Ohga等人，1989年）之后，我们分析了C3H-lpr小鼠LN细胞cDNA文库中的Vβ基因序列。在B6-lpr的32个βcDNA中有11个β链cDNA，在C3H-lpr的55个βcDNA中有24个β链cDNA被发现含有具有开放阅读框的序列，这些序列可能编码功能性TcRβ链。这些小鼠cDNA文库中信息的频率与使用Vβ3和Vβ5特异性探针进行的RNA印迹分析结果一致。值得注意的是，B6-lpr中36%的功能性β链mRNA和C3H-lpr中50%的βmRNA表达Vβ8基因家族。正如Singer等人（1986年）所报道的，当比较C3H-lpr、B6-lpr和MRL-lpr的LN细胞之间的TcR Vβ基因表达时，B6-lpr（H-2b）LN细胞中除Vβ8基因家族之外的Vβ基因使用情况与C3H-lpr（H-2k）和MRL-lpr（H-2k）中的情况有显著差异。此处呈现的结果表明，Vβ基因的使用受到lpr小鼠遗传背景的严重影响，这与正常小鼠类似，但Vβ8基因家族的优先使用是lpr基因诱导细胞群体中的一个共同结构特征。
