STOCHASTIC-CONTROL OF ANTI-SM AUTOANTIBODIES IN MRL/MP-LPR/LPR MICE
STOCHASTIC-CONTROL OF ANTI-SM AUTOANTIBODIES IN MRL/MP-LPR/LPR MICE
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DOI：
10.1172/jci113123
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发表时间：
1987-09-01
影响因子：
15.9
通讯作者：
COHEN, PL
中科院分区：
文献类型：
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作者：
EISENBERG, RA;CRAVEN, SY;COHEN, PL
MRL/Mp-lpr/lpr自身免疫小鼠一致地显示出约系统性红斑狼疮标志物自身抗体抗Sm.在本报告中，我们表明，未能找到抗Sm抗体在四分之三的5个月大的MRL/lpr小鼠是不是一个不敏感的检测伪像，而是小鼠分为两个群体，就其抗Sm阳性。基于广泛的分析，抗Sm阳性的发病率在5个月大的小鼠，根据其笼的居住，我们没有发现任何证据的遗传，环境，或父母的影响的倾向，个别动物成为抗Sm阳性。此外，小鼠的性别，其Sm抗原水平，或其生存时间与抗Sm抗体无关，也不是任何父母的抗Sm抗体状态。一些动物在5个月龄后成为抗Sm阳性，但这比5个月龄前成为阳性的可能性要小。最后，对205只自身免疫C57 BL/6-lpr/lpr小鼠的调查证实了这种自身抗体应答的MRL背景的独特性。这些结果共同表明，抗Sm抗体的可能性是在遗传控制下，但这种能力在个体动物的表达是由随机事件。我们进一步假设，这种随机过程可能涉及特定免疫球蛋白可变区基因的表达，结合广泛的体细胞突变或正反馈扩增机制，这将使最初的单克隆反应转化为最终的多克隆反应。
MRL/Mp-lpr/lpr autoimmune mice consistently show an .apprx. 25% incidence of the systemic lupus eyrthematosus marker autoantibody anti-Sm. In the present report, we show that the failure to find anti-Sm antibodies in three-quarters of 5-mo-old MRL/lpr mice was not an artifact of an insensitive assay, but rather that the mice fell into two populations as regards their anti-Sm positivity. Based on an extensive analysis of the incidence of anti-Sm positivity in 5-mo-old mice according to their cage of residence, we found no evidence for genetic, environmental, or parental influences on the propensity of an individual animal to become anti-Sm positive. Also, the gender of the mouse, its Sm antigen levels, or its length of survival were not related to anti-Sm antibody, nor was the anti-Sm antibody status of either parent. Some animals became anti-Sm positive after 5 mo of age, but this was less likely than becoming positive before 5 mo of age. Finally, a survey of 205 autoimmune C57BL/6-lpr/lpr mice confirmed the uniqueness of the MRL background for this autoantibody response. These results together indicate that the possibility of making anti-Sm antibodies is under genetic control, but that the expression of this capability in an individual animal is governed by stochastic events. We hypothesize further that such random processes may involve the expression of particular immunoglobulin variable-region genes combined with mechanisms of extensive somatic mutation or positive feedback amplification, which would transmute an initial monoclonal response into an eventual polyclonal one.