Influenza virus infection causes global respiratory tract B cell response modulation via innate immune signals
Influenza virus infection causes global respiratory tract B cell response modulation via innate immune signals
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DOI：
10.4049/jimmunol.178.3.1457
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发表时间：
2007-02-01
影响因子：
4.4
通讯作者：
Baumgarth, Nicole
中科院分区：
文献类型：
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作者：
Chang, W. L. William;Coro, Elizabeth S.;Baumgarth, Nicole
原发B细胞反应的诱导需要抗原和T细胞共刺激信号的存在。先天信号进一步增强了B细胞的激活。这种先天免疫信号的确切性质和动力学以及它们的功能效应尚不清楚。这项研究表明，流感病毒诱导的I型干扰素是感染48h内影响局部B细胞的主要先天刺激。它改变了B细胞的转录图谱，并选择性地将它们困在区域淋巴结中，推测是通过上调CD69来实现的。有些自相矛盾的是，先天B细胞刺激抑制了BCR介导的刺激后区域淋巴B细胞克隆性扩张的能力。这种抑制是由于流感感染后诱导的IFNR信号非依赖性B细胞内源性调节以及WNR依赖性B细胞外源性调节所致。IFNR介导的信号也减少了B细胞向各种趋化药物的迁移。B细胞对CCR7配体缺乏反应性，MHC-II类抗原加工/提呈相关基因和CD40表达没有改变或减少，B细胞不能诱导初始的CD4T细胞增殖。相反，他们显示了一组非经典MHC分子的表达增加，这些分子促进了与伽马增量T细胞和NK T细胞的相互作用。我们得出结论，I型干扰素是流感感染后主要的第三种B细胞信号，导致B细胞早期被困在区域淋巴结中，在同源T细胞帮助很少的时候，增强了它们与先天免疫细胞相互作用的倾向，以获得非同源刺激。
Induction of primary B cell responses requires the presence of Ag and costimulatory signals by T cells. Innate signals further enhance B cell activation. The precise nature and kinetics of such innate immune signals and their functional effects are unknown. This study demonstrates that influenza virus-induced type I IFN is the main innate stimulus affecting local B cells within 48 h of infection. It alters the transcriptional profile of B cells and selectively traps them in the regional lymph nodes, presumably via up-regulation of CD69. Somewhat paradoxically, innate B cell stimulation inhibited the ability of regional lymph node B cells to clonally expand following BCR-mediated stimulation. This inhibition was due to IFNR-signaling independent B cell intrinsic, as well as WNR-dependent B cell extrinsic, regulation induced following influenza infection. IFNR-mediated signals also reduced B cell migration to various chemotactic agents. Consistent with the lack of responsiveness to CCR7 ligands, unaltered or reduced expression of MHC class II and genes associated with MHC class II Ag processing/presentation and CD40, B cells were unable to induce proliferation of naive CD4 T cells. Instead, they showed increased expression of a subset of nonclassical MHC molecules that facilitate interaction with gamma delta T cells and NK T cells. We conclude that type I IFN is the main "third" B cell signal following influenza infection causing early trapping of B cells in regional lymph nodes and, at a time when cognate T cell help is rare, enhancing their propensity to interact with innate immune cells for noncognate stimulation.