Autoantigen glycoprotein 70 expression is regulated by a single locus, which acts as a checkpoint for pathogenic anti-glycoprotein 70 autoantibody production and hence for the corresponding development of severe nephritis, in lupus-prone BXSB mice

被引:30
作者
Haywood, MEK
Vyse, TJ
McDermott, A
Thompson, EM
Ida, A
Walport, MJ
Izui, S
Morley, BJ
机构
[1] Imperial Coll Sch Med, Rheumatol Sect, London W12 0NN, England
[2] St Marys Hosp, Dept Histopathol, London, England
[3] Ctr Med Univ Geneva, Dept Pathol, Geneva, Switzerland
关键词
D O I
10.4049/jimmunol.167.3.1728
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Retroviral envelope glycoprotein gp70 is present in the sera of immunologically normal and autoimmune-prone strains of mice. However, only lupus-prone mice spontaneously develop gp70-anti-gp70 immune complexes (gp70IC), and these have been implicated in the development of nephritis. We investigated the genetic factors that affect the production of both free serum gp70 and gp70IC in the lupus-prone BXSB mouse strain by analyzing (BXSB X (C57BL/10 X BXSB)F-1)- and (C57BL/10 X (C57BL/10 X BXSB)F-1)-backcrossed male mice. Production of gp70 mapped to a single major locus located on chromosome 13 (Bxs6) with a maximum log likelihood of the odds of 36.7 (p = 1.6 X 10(-38)). The level of gp70IC was highly dependent on Bxs6-related gp70 production, and high titer autoantibody production only occurred when serum gp70 levels were greater than a threshold value of similar to4.0 mug/ml. The subdivision of the (BXSB X (C57BL/10 X BXSB)F-1)-backcrossed mice into those homozygous or heterozygous for Bxs6 enabled a remarkable association to be observed between high levels of gp70IC and severe nephritis in the Bxs6 homozygote population. A further mapping study in these two subgroups identified a previously unrecognized interval associated with the production of autoantibodies.
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页码:1728 / 1733
页数:6
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