Izui S, Higaki M, Morrow D, Merino R
Department of Pathology, University of Geneva, Switzerland.
Eur J Immunol. 1988 Jun;18(6):911-5. doi: 10.1002/eji.1830180612.
The Y chromosome of the BXSB mouse has been shown to be responsible for the acceleration of lupus-like autoimmune syndrome in inbred BXSB mice and in their F1 hybrids with NZB or NZW mice. To further define the role of this as yet unidentified gene linked to the BXSB Y chromosome, designated Yaa (Y chromosome-linked autoimmune acceleration), the Y chromosome was transferred from the BXSB strain to nonautoimmune C57BL/6 (B6) mice. The effect of the Yaa gene on the autoantibody formation and the development of glomerulonephritis was investigated in B6 mice and in their F1 hybrids with NZW mice. The presence of the BXSB Y chromosome was not able to induce significant autoimmune responses in B6 mice. However, (NZW x B6)F1 males bearing the BXSB Y chromosome developed a severe lupus-like autoimmune syndrome, as documented by the production of anti-DNA antibodies and gp70-anti-gp70 immune complexes and the development of lethal lupus nephritis. Both sexes of (NZW x B6)F1 hybrids without the BXSB Y chromosome were essentially normal. Our results suggest that (a) the BXSB Y chromosome by itself is not sufficient to initiate autoimmune responses in nonautoimmune B6 mice, and (b) it is able to induce autoimmune responses in mice potentially capable of developing the disease, but whose autosomal abnormality by itself is not sufficient to develop autoimmune diseases.
已证明BXSB小鼠的Y染色体可导致近交系BXSB小鼠及其与NZB或NZW小鼠的F1杂种中狼疮样自身免疫综合征加速发展。为了进一步确定这个与BXSB Y染色体连锁的尚未鉴定的基因（命名为Yaa，即Y染色体连锁自身免疫加速基因）的作用，将Y染色体从BXSB品系转移到非自身免疫性的C57BL/6（B6）小鼠。在B6小鼠及其与NZW小鼠的F1杂种中研究了Yaa基因对自身抗体形成和肾小球肾炎发展的影响。BXSB Y染色体的存在未能在B6小鼠中诱导显著的自身免疫反应。然而，携带BXSB Y染色体的（NZW×B6）F1雄性小鼠出现了严重的狼疮样自身免疫综合征，表现为产生抗DNA抗体和gp70-抗gp70免疫复合物以及致命性狼疮肾炎的发展。没有BXSB Y染色体的（NZW×B6）F1杂种的两性基本正常。我们的结果表明：（a）BXSB Y染色体本身不足以在非自身免疫性B6小鼠中引发自身免疫反应；（b）它能够在可能发展该疾病但自身常染色体异常不足以发展自身免疫性疾病的小鼠中诱导自身免疫反应。
