Wild-derived mouse strains, a valuable model to study B cell responses.
Wild-derived mouse strains, a valuable model to study B cell responses.
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野生小鼠品系，是研究 B 细胞反应的有价值的模型。
DOI：
10.1016/j.molimm.2008.07.027
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发表时间：
2009
影响因子：
3.6
通讯作者：
D. Rueff‐Juy
中科院分区：
文献类型：
--
作者：
Aude Thiriot;A. Drapier;S. Mémet;C. Fitting;Aude Sturny;J. Cavaillon;P. Cazenave;A. Freitas;D. Rueff‐Juy
在本报告中，我们重新研究了7种野生来源的小鼠菌株对各种toll样受体配体（TLR-L）的B细胞反应性。我们发现其中2个，即PWK和STF对大多数TLR-L的B细胞增殖反应存在严重缺陷。然而，它们的巨噬细胞反应在很大程度上未受影响，这表明TLR通路的调节在B细胞和巨噬细胞中是不同的。我们还发现，抗cd40单克隆抗体挽救了PWK和STF B细胞对CpG的低增殖反应。另一方面，CpG与LPS协同作用诱导STF B细胞高水平增殖，而STF B细胞对LPS没有反应。在体外，细胞因子或免疫球蛋白（Ig）的产生比单独使用LPS或CpG的增殖反应受到的损害更小。在STF B细胞中，体外TLR4或TLR9信号传导后，ERK、P38和JNK通路均受到影响。此外，虽然Ig分泌细胞和血清igg的基础水平与对照小鼠相似，但对TI和TD抗原的抗体反应受到严重影响，主要是在STF小鼠中。因此，我们的发现强调了野生来源的小鼠品系和TLR-L在研究B细胞生理学中的相关性。
In the present report, we revisited the B cell responsiveness of 7 wild-derived mouse strains to various toll-like receptor ligands (TLR-L). We found that 2 of them, namely PWK and STF presented profound defects in B cell proliferative responses to most of the TLR-L. Yet, their macrophage responses were largely unaffected, suggesting that regulation of TLR pathways are distinct in B cells and macrophages. We also showed that, anti-CD40 mAbs rescued the low proliferative responses to CpG in both PWK and STF B cells. In the other hand, CpG synergized with LPS to induce high levels of proliferation in STF B cells, which did not respond to LPS alone. Cytokine or immunoglobulin (Ig) productions, in vitro, were less impaired than the proliferative responses to LPS or CpG alone. In STF B cells, both ERK, P38 and JNK pathways were affected following in vitro TLR4 or TLR9 signaling. Moreover, while the basal levels of Ig secreting cells and of serum Igs were similar to that of control mice, antibody responses to both TI and TD antigens were severely affected, mainly in STF mice. Our findings therefore highlight the relevance of wild-derived mouse strains and TLR-L to study B cell physiology.