Studies on the Mechanism of Induction of Autoimmune Disease by the Novel Lymphoproliferation gene, lpr^<cg>

在实验动物研究中心饲养的CBA/KlJms（CBA）群中发现了几只全身淋巴结病小鼠。通过将这些患病小鼠杂交，建立了一种新的突变小鼠品系，其在5月龄内发生大量淋巴样增生的发生率为100%。遗传学分析表明，淋巴结病是由一个常染色体隐性基因控制的，该基因与lpr等位，但可与1号染色体上的qld互补，诱导淋巴结肿胀（LN）。因此，将新的突变基因命名为lpr^<cg>，并将突变株命名为CBA-lpr^<cg>/lpr^<cg>（CBA-lpr^<cg>）。突变小鼠出现高丙种球蛋白血症和各种自身抗体，其肿胀的LN由Thy-1 ^+ CD 4 ^-CD 8 ^-B220^+淋巴细胞或“双阴性（DN）”T细胞组成。从CBA-lpr^小鼠<cg>到CBA-+/+（CBA-+）小鼠的骨髓（BM）转移引起自身抗体形成，但不引起淋巴结病。我们开发了一种简单的全LN移植技术， ...更多信息 到，证明lpr + <cg>DN T细胞可以归巢到lpr+<cg>和lpr + LN中，但不能归巢到gld和+ LN中。因此，lpr和gld基因在LN位点的表型表达彼此不同。来自lpr^和gld杂合<cg>小鼠（1 pr ^<cg>-gld小鼠）的LN允许1 pr ^<cg>DN T细胞归巢，支持lpr^和gld之间的协同性<cg>。尽管lpr^ -gld小鼠的淋巴结病变较轻<cg>，但扩增的LN细胞显示出与lpr^和gld小鼠相同的表面标记模式<cg>。在lpr和gld小鼠中，血清免疫球蛋白和IgM类自身抗体水平升高，但IgG类自身抗体水平不升高<cg>。ILRO和lpr^ -gld小鼠的血清IgG<cg>在白细胞介素3依赖性细胞系中诱导白细胞介素3，与严重程度相关。淋巴结病建立无胸腺lpr^<cg>小鼠以研究胸腺在lpr^诱导淋巴结病中的作用<cg>。LN肿胀发生与胸腺移植物，无论其遗传背景，但不是没有他们，表明胸腺是必不可少的BM细胞异常分化成DN T细胞。lpr^<cg>基因被定位在19号染色体上。少

Several mice with generalized lymphadenopathy were found in the CBA/KlJms (CBA) colony maintained at the Laboratory Animal Research Center. A new mutant strain of mice that develop massive lymphoid hyperplasia at 100% incidence within 5 months of age was established by crossing these diseased mice. Genetic analyses revealed that lymphadenopathy is controlled by a single autosomal recessive gene which is allelic with lpr but can complement qld on chromosome 1 in the induction of swelling of lymph nodes (LN). Thus, the new mutant gene was named lpr^<cg> and the mutant strain was designa Led CBA-lpr^<cg>/lpr^<cg> (CBA-lpr^<cg>). Mutant mice developed hypergammaglobulinemia and various autoantibodies, and their swelled LN were composed of Thy-l^+CD4^-CD8^-B220^+ lymphoid cells or "double-negatice (DN)" T cells. Bone marrow (BM) transfer from CBA-lpr^<cg> to CBA-+/+ (CBA-+) mice caused autoantibody formation but not lymphadenopathy. We developed a simple technique for whole LN transplantati … More on to, demonstrate that lpr^<cg> DN T cells could home into lpr^<cg> and lpr LN but not into gld and + LN. Therefore, the lpr and gld genes are different from each other in the phenotype expression at the LN site. LN from mice heterozygous for both lpr^<cg> and gld (1pr^<cg>-gld mice) allowed homing of 1pr^<cg> DN T cells in support of the cooperativity between lpr^<cg> and gld. Despite milder lymphadenopathy in lpr^<cg>-gld mice, the expanding LN cells showed the same pattern of surface markers as that in lpr^<cg> and gld mice. Serum immunoglobulin and autoantibody levels of IgM class but not those of IgG class were elevated in lpr^<cg> and gld mice. Serum IgG from ILRO and lpr^<cg>-gld mice induced interleukin 3 in an interleukin 3-dependent cell line in relation to the severity. of lymphadenopathy. Athymic lpr^<cg> mice were constructed to investigate the role of the thymus in induction of lymphadenopathy by lpr^<cg>. LN swelling occurred with thymus grafts regardless of their genetic backgrounds but not without them, indicating that the thymus is essential for abnormal differentiation of BM cells into DN T cells. The lpr^<cg> gene is being mapped on chromosome 19. Less