H-2-LINKED CONTROL OF THE YAA GENE-INDUCED ACCELERATION OF LUPUS-LIKE AUTOIMMUNE-DISEASE IN BXSB MICE
H-2-LINKED CONTROL OF THE YAA GENE-INDUCED ACCELERATION OF LUPUS-LIKE AUTOIMMUNE-DISEASE IN BXSB MICE
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DOI：
10.1002/eji.1830220202
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发表时间：
1992-02-01
影响因子：
5.4
通讯作者：
IZUI, S
中科院分区：
文献类型：
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作者：
MERINO, R;FOSSATI, L;IZUI, S
雄性BXSB小鼠（H-2b，I-E-）中狼疮样自身免疫性疾病的加速发展与位于其Y染色体上的突变基因（命名为Yaa）的存在相关。 为了研究H-2b单倍型和/或I-E分子表达的缺乏是否在Yaa连锁的自身免疫性疾病的加速中起任何作用，通过回交程序产生I-E+ BXSB.H-2d同源株。 我们比较了新型BXSB.H-2d（I-E+）品系与BXSB.H-2b（I-E-）和BXSB.H-2b/d（I-E+）杂合子小鼠中自身免疫性疾病的发展。 雄性BXSB.H-2d（I-E+）小鼠仅表现出有限的自身抗体产生和较低的肾小球肾炎发生率，并且存活率显著延长，这与具有H-2b和H-2d单倍型的雌性BXSB小鼠基本相同。 然而，BXSB.H-2b/d（I-E+）杂合子雄性小鼠发生了与常规BXSB.H-2b（I-E-）雄性小鼠相当的加速性疾病。 这些结果表明，I-E分子的表达和随后的I-E反应性T细胞的克隆缺失或无反应性似乎不负责预防BXSB.H-2d（I-E+）雄性小鼠中的加速自身免疫性疾病。 Yaa基因诱导的狼疮样自身免疫性疾病的加速受H-2复合体内或与H-2复合体紧密相连的基因调节的发现强调了BXSB小鼠中主要组织相容性复合体的关键作用和自身免疫性疾病的多基因性质。
The accelerated development of lupus-like autoimmune disease in male BXSB mice (H-2b, I-E-) is associated to the presence of a mutant gene, designated Yaa, located on their Y chromosome. To investigate whether the H-2b haplotype and/or the lack of expression of I-E molecules play any role in the Yaa-linked acceleration of autoimmune disease, an I-E+ BXSB.H-2d congenic strain was created by backcross procedures. We compared the development of autoimmune disease in the novel BXSB.H-2d (I-E+) strain to that of BXSB.H-2b (I-E-) and BXSB.H-2b/d (I-E+) heterozygous mice. Male BXSB.H-2d (I-E+) mice exhibited only a limited production of autoantibodies and a lower incidence of glomerulonephritis with a markedly prolonged survival rate, which were essentially identical to those of female BXSB mice of both-H-2b and H-2d haplotypes. However, BXSB.H-2b/d (I-E+) heterozygous males developed an accelerated disease comparable to that of conventional BXSB.H-2b (I-E-) male mice. These results indicate that the expression of I-E molecules and consequent clonal deletion or anergy of I-E reactive T cells does not appear to be responsible for the prevention of accelerated autoimmune disease in BXSB.H-2d (I-E+) male mice. The finding that the Yaa gene-induced acceleration of lupus-like autoimmune disease is modulated by gene(s) within or closely linked to the H-2 complex underlines the crucial role of the major histocompatibility complex and the polygenetic nature of autoimmune disease in BXSB mice.