T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells.
T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells.
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DOI：
10.1016/j.immuni.2008.06.009
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发表时间：
2008-08-15
期刊：
影响因子：
32.4
通讯作者：
Shlomchik, Mark J.
中科院分区：
文献类型：
--
作者：
Herlands, Robin A.;Christensen, Sean R.;Sweet, Rebecca A.;Hershberg, Uri;Shlomchik, Mark J.
在狼疮倾向的MRL-lpr/lpr（MRL-lpr）背景下，AM 14类风湿因子（RF）B细胞被激活，分化成浆母细胞，并在卵泡外经历体细胞超变。使用多种策略来损害T细胞，我们发现这种AM 14 B细胞活化不需要T细胞，但可以由它们调节。在体外，当T细胞不存在时，IgG抗染色质刺激AM 14 B细胞增殖需要信号转导衔接子MyD 88。然而，Toll样受体（TLR）在体内AM 14 B细胞活化中的作用尚未研究。我们发现AM14 B细胞的活化、扩增和分化依赖于MyD 88;然而，缺乏TLR7或TLR9的小鼠显示出部分缺陷，表明这些受体的复杂作用。某些自身反应性B细胞的T-非依赖性活化（其反而可以通过内源性TLR配体获得刺激）可能是产生典型自身抗体的初始步骤。
On the lupus-prone MRL-lpr/lpr (MRL-lpr) background AM14 rheumatoid factor (RF) B cells are activated, differentiate into plasmablasts, and undergo somatic hypermutation outside of follicles. Using multiple strategies to impair T cells, we found that such AM14 B cell activation did not require T cells, but could be modulated by them. In vitro, the signaling adaptor MyD88 is required for IgG anti-chromatin to stimulate AM14 B cell proliferation when T cells are absent. However the roles of Toll-like receptors (TLRs) in AM14 B cell activation in vivo have not been investigated. We found that activation, expansion and differentiation of AM14 B cells depended on MyD88; however, mice lacking either TLR7 or TLR9 displayed partial defects, indicating complex roles for these receptors. T-independent activation of certain autoreactive B cells, which instead can gain stimuli via endogenous TLR ligands, may be the initial step in the generation of canonical autoantibodies.
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影响因子：
32.4
作者：
Kawai, T;Adachi, O;Akira, S
通讯作者：
Akira, S
DOI：
10.1073/pnas.88.24.11271
发表时间：
1991-12-01
影响因子：
11.1
作者：
ADAMS, S;LEBLANC, P;DATTA, SK
通讯作者：
DATTA, SK
影响因子：
5.4
作者：
Herlands, Robin A.;William, Jacqueline;Shlomchik, Mark J.
通讯作者：
Shlomchik, Mark J.
影响因子：
32.4
作者：
JACOBSON, BA;PANKA, DJ;MARSHAKROTHSTEIN, A
通讯作者：
MARSHAKROTHSTEIN, A
影响因子：
4.4
作者：
Good, Kim L.;Bryant, Vanessa L.;Tangye, Stuart G.
通讯作者：
Tangye, Stuart G.