Eisenberg R A, Craven S Y, Fisher C L, Morris S C, Rapoport R, Pisetsky D S, Cohen P L
Department of Medicine, University of North Carolina, Chapel Hill 27599-7280.
Clin Exp Rheumatol. 1989 Sep-Oct;7 Suppl 3:S35-40.
We have investigated the influence of background genes in the MRL strain, as compared to C57BL/6, on the induction of autoimmunity in homozygous lpr/lpr mice. We have concentrated on two autoantibodies, anti-Sm and anti-chromatin. The propensity to make anti-Sm is controlled by dominant genes from the MRL background. However, the prevalence of this response is under the control of additional recessive genes. The anti-chromatin response is found in both MRL/Mp-lpr/lpr and in C57BL/6-lpr/lpr mice, but it appears earlier and in higher titers in the former strain. This high responder effect is controlled by dominant genes. In F1 mice between these two strains, both anti-Sm and anti-chromatin antibodies preferentially use the b Igh allotype from the low responder B6/lpr parent. In addition, in the progeny of backcross of the F1 to the MRL/lpr strain, the production of both anti-Sm and anti-chromatin is linked to the b allotype. These results demonstrate the contribution of dominant genes from the MRL background on the induction of severe autoimmunity. They also suggest that the B6 background expresses an Igh allotype particularly amenable to autoantibody production, in spite of the relatively mild SLE-like syndrome in this strain.
我们研究了与C57BL/6相比，MRL品系的背景基因对纯合lpr/lpr小鼠自身免疫诱导的影响。我们重点关注了两种自身抗体，即抗Sm抗体和抗染色质抗体。产生抗Sm抗体的倾向受来自MRL背景的显性基因控制。然而，这种反应的发生率受其他隐性基因的调控。在MRL/Mp-lpr/lpr和C57BL/6-lpr/lpr小鼠中均发现了抗染色质反应，但在前一种品系中出现得更早且滴度更高。这种高反应效应受显性基因控制。在这两个品系之间的F1小鼠中，抗Sm抗体和抗染色质抗体都优先使用来自低反应性B6/lpr亲本的b Igh同种异型。此外，在F1与MRL/lpr品系回交的后代中，抗Sm抗体和抗染色质抗体的产生都与b同种异型相关。这些结果证明了来自MRL背景的显性基因对严重自身免疫诱导的作用。它们还表明，尽管该品系中SLE样综合征相对较轻，但B6背景表达的Igh同种异型特别有利于自身抗体的产生。
