The lupus susceptibility locus Sle1 breaches peripheral B cell tolerance at the antibody-forming cell and germinal center checkpoints.
The lupus susceptibility locus Sle1 breaches peripheral B cell tolerance at the antibody-forming cell and germinal center checkpoints.
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DOI：
10.4049/jimmunol.0804215
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发表时间：
2009-11-01
期刊：
影响因子：
--
通讯作者：
Rahman ZS
中科院分区：
文献类型：
--
作者：
Vuyyuru R;Mohan C;Manser T;Rahman ZS
We have described a line of VH “knockin” mice termed HKIR in which the transgenic Igh locus partially encodes “dual reactive” anti-chromatin and anti-arsonate (Ars) BCRs. HKIR B cells termed canonical, expressing a particular Vκ light chain, evade central tolerance by down regulating BCR levels. Canonical HKIR B cells can be recruited into the primary GC and AFC compartments via Ars immunization. However, their participation in the GC response rapidly wanes and they do not efficiently contribute to the memory compartment, indicating they are regulated by a GC tolerance checkpoint. We analyzed the influence of the Sle1 genetic interval, shown to break tolerance of chromatin reactive B cells, on the behavior of HKIR B cells during the anti-Ars response. Canonical B cells from congenic HKIR.Sle1 mice gave rise to elevated short and long-lived AFC responses, and the attenuated GC and memory responses characteristic of these B cells were relieved in adoptive, wild type recipients. HKIR GC B cells containing Sle1 expressed increased levels of Bcl-2 and c-FLIP and decreased levels of Fas RNA as compared to HKIR controls, suggesting direct alteration of the regulation of the GC response by Sle1. High titers of canonical and anti-dsDNA antibodies spontaneously developed in many aged HKIR.Sle1 mice. Together, these data indicate that Sle1 perturbs the action of peripheral tolerance checkpoints operative on antinuclear antigen B cells in both the AFC and GC pathways in a cell autonomous fashion.
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影响因子：
3.2
作者：
Jiang, Y;Hirose, S;Shirai, T
通讯作者：
Shirai, T
影响因子：
30.5
作者：
Fukuyama, H;Nimmerjahn, F;Ravetch, JV
通讯作者：
Ravetch, JV
影响因子：
15.9
作者：
Cappione, A;Anolik, JH;Sanz, I
通讯作者：
Sanz, I
影响因子：
56.9
作者：
Kumar, Kirthi Raman;Li, Liunan;Mohan, Chandra
通讯作者：
Mohan, Chandra
DOI：
10.1084/jem.177.4.999
发表时间：
1993-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gay D;Saunders T;Camper S;Weigert M
通讯作者：
Weigert M