Early requirement for B cells for development of spontaneous autoimmune thyroiditis in NOD.H-2h4 mice

被引:59
作者
Braley-Mullen, H
Yu, SG
机构
[1] Univ Missouri, Dept Internal Med, Columbia, MO 65212 USA
[2] Univ Missouri, Dept Med Microbiol & Immunol, Columbia, MO 65212 USA
[3] Vet Adm Res Serv, Columbia, MO 65212 USA
关键词
D O I
10.4049/jimmunol.165.12.7262
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
B cells are known to play an important role in the pathogenesis of several autoimmune diseases. NOD.H-2h4 mice develop spontaneous autoimmune thyroiditis (SAT) and anti-mouse thyroglobulin (MTg) autoantibodies, the levels of which correlate closely with the severity of thyroid lesions. NOD.H-2h4 mice genetically deficient in B cells (NOD.K mu (null)) or rendered B cell-deficient by treatment from birth with anti-IgM develop minimal SAT. B cells were required some time in the first 4-6 wk after birth, because NOD.K mu (null) or NOD.H-2h4 mice did not develop SAT when they were reconstituted with B cells as adults, The requirement for B cells was apparently not solely to produce anti-MTg autoantibodies, because passive transfer of anti-MTg Ab did not enable B cell-deficient mice to develop SAT, and mice given B cells as adults produced autoantibodies but did not develop SAT. B cell-deficient mice developed SAT if their T cells developed from bone marrow precursors in the presence of B cells. Because B cells are required early in life and their function cannot be replaced by anti-MTg autoantibodies, B cells may be required for the activation or selection of autoreactive T cells. These autoreactive T cells are apparently unable to respond to Ag if B cells are absent in the first 4-6 wk after birth.
引用
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页码:7262 / 7269
页数:8
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