Merino R, Shibata T, De Kossodo S, Izui S
Department of Pathology, Centre Medical Universitaire, Geneva, Switzerland.
Eur J Immunol. 1989 Nov;19(11):2131-7. doi: 10.1002/eji.1830191124.
The Yaa gene (Y chromosome-linked autoimmune acceleration), linked to the BXSB/MpJ Y chromosome, and the autosomal recessive lpr (lymphoproliferation) gene have been shown to accelerate the progression of the lupus-like autoimmune syndrome in the BXSB and MRL strains, respectively. To compare more directly the role of the Yaa and lpr genes in the development of the autoimmune syndrome, the Y chromosome of BXSB mice was transferred to MRL mice by backcross procedures, and the effect of the Yaa gene on the autoantibody formation and the development of lupus-like nephritis in MRL mice was investigated in comparison with those bearing the lpr mutation. The Yaa gene as well as the lpr gene were able to shorten the life span of MRL mice as a result of the accelerated development of lethal lupus-like nephritis. However, the acceleration promoted by the Yaa gene (50% mortality rate: 12 months) was less severe than that induced by the lpr gene (50% mortality rate: 7 months). This may be related to the finding that the lpr gene enhanced the production of a large spectrum of autoantibodies, including anti-DNA, rheumatoid factors and anti-gp70, and of cryoglobulins, whereas only anti-gp70 production among the autoantibodies studies was markedly enhanced by the Yaa gene. The selective autoimmune accelerating effect of the Yaa gene was similarly observed in (NZW X MRL)F1 hybrid mice. Our results suggest that the Yaa gene, unlike the lpr gene, exhibits selective autoimmune accelerating activity, but as a result of increased formation of certain nephritogenic autoantibodies such as anti-gp70 antibodies, the Yaa gene is able to accelerate the progression of lupus-like nephritis in lupus-prone mice.
与BXSB/MpJ Y染色体相关的Yaa基因（Y染色体连锁自身免疫加速基因）和常染色体隐性lpr（淋巴细胞增殖）基因，已分别被证明可加速BXSB和MRL品系中狼疮样自身免疫综合征的进展。为了更直接地比较Yaa和lpr基因在自身免疫综合征发展中的作用，通过回交程序将BXSB小鼠的Y染色体转移到MRL小鼠中，并与携带lpr突变的小鼠相比，研究Yaa基因对MRL小鼠自身抗体形成和狼疮样肾炎发展的影响。由于致死性狼疮样肾炎的加速发展，Yaa基因和lpr基因均能够缩短MRL小鼠的寿命。然而，Yaa基因促进的加速作用（50%死亡率：12个月）不如lpr基因诱导的严重（50%死亡率：7个月）。这可能与以下发现有关：lpr基因增强了包括抗DNA、类风湿因子和抗gp70在内的多种自身抗体以及冷球蛋白的产生，而在研究的自身抗体中，Yaa基因仅显著增强了抗gp70的产生。在（NZW×MRL）F1杂交小鼠中同样观察到了Yaa基因的选择性自身免疫加速作用。我们的结果表明，与lpr基因不同，Yaa基因表现出选择性自身免疫加速活性，但由于某些致肾炎自身抗体如抗gp70抗体的形成增加，Yaa基因能够加速狼疮易感小鼠中狼疮样肾炎的进展。
