Entry of B cell receptor into signaling domains is inhibited in tolerant B cells

被引:78
作者
Weintraub, BC
Jun, JE
Bishop, AC
Shokat, KM
Thomas, ML
Goodnow, CC
机构
[1] Australian Natl Univ, John Curtin Sch Med Res, Med Genome Ctr, Australian Canc Res Fdn,Genet Lab, Canberra, ACT 2601, Australia
[2] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA
[3] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA
[4] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA
关键词
B cell antigen receptor signaling; tyrosine phosphorylation; membrane raft; self-tolerance; anergy;
D O I
10.1084/jem.191.8.1443
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Signal transduction through the B cell antigen receptor (BCR) is altered in B cells that express a receptor that recognizes self-antigen. To understand the molecular basis for the change in signaling in autoreactive B cells, a transgenic model was used to isolate a homogeneous population of tolerant B lymphocytes. These cells were compared with a similar population of naive B lymphocytes. We show that the BCR from naive B cells enters a detergent-insoluble domain of the cell within 6 s after antigen binding, before a detectable increase in BCR phosphorylation. This fraction appears to be important for signaling because it is enriched for lyn kinase but lacks CD45 tyrosine phosphatase and because the BCR that moves into this domain becomes more highly phosphorylated. Partitioning of the BCR into this fraction is unaffected by src family kinase inhibition. Tolerant B cells do not efficiently partition the BCR into the detergent-insoluble domain, providing an explanation for their reduced tyrosine kinase activation and calcium nux in response to antigen. These results identify an early, regulated step in antigen receptor signaling and self-tolerance.
引用
收藏
页码:1443 / 1448
页数:6
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