The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system.
The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system.
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DOI：
10.1016/j.bbi.2010.10.002
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发表时间：
2011-07
影响因子：
15.1
通讯作者：
Irani, David N.
中科院分区：
文献类型：
--
作者：
Rainey-Barger, Emily K.;Rumble, Julie M.;Lalor, Stephen J.;Esen, Nilufer;Segal, Benjamin M.;Irani, David N.
关键词：
进行性多灶性白质脑病病例可发生在接受B细胞耗竭性抗CD20抗体利妥昔单抗治疗的患者中，这突出了中枢神经系统（CNS）B细胞监测的重要性。淋巴样趋化因子CXCL 13对于外周淋巴组织的B细胞募集和功能组织是关键的，并且CXCL 13水平通常在发炎的CNS中升高。为了更直接地研究CXCL 13在CNS B细胞迁移中的作用，检查了其在感染性和炎性脱髓鞘疾病的动物模型中的作用。在急性甲病毒脑炎期间，病毒清除取决于抗病毒抗体的局部作用，脑组织中的CXCL 13水平和B细胞数量随时间增加。然而，令人惊讶的是，CXCL 13缺陷型动物显示正常的CNS B细胞募集、未改变的CNS病毒复制和清除以及完整的外周抗病毒抗体应答。在实验性自身免疫性脑脊髓炎（EAE）期间，CXCL 13的CNS水平随着症状出现而增加，并且与对照动物相比，在CXCL 13缺陷小鼠的CNS浸润物中鉴定出相等数量的B细胞。然而，CXCL13缺陷型小鼠不能维持致病性抗髓鞘T细胞应答，这与它们已知的发展更多自限性EAE的倾向一致。这些数据表明，在两种模型中，CXCL 13均对CNS B细胞募集不利。在依赖于病原体特异性B细胞应答的CNS感染范例中，疾病过程不受CXCL 13的影响，而当髓鞘特异性CD4+ T细胞驱动CNS病理时，疾病过程被CXCL 13增强和延长。因此，CXCL 13可能是某些神经炎性疾病的治疗靶点，但不是通过阻断B细胞向CNS的募集。
Cases of progressive multifocal leukoencephalopathy can occur in patients treated with the B cell depleting anti-CD20 antibody, rituximab, highlighting the importance of B cell surveillance of the central nervous system (CNS). The lymphoid chemokine, CXCL13, is critical for B cell recruitment and functional organization of peripheral lymphoid tissues, and CXCL13 levels are often elevated in the inflamed CNS. To more directly investigate the role of CXCL13 in CNS B cell migration, its role in animal models of infectious and inflammatory demyelinating disease was examined. During acute alphavirus encephalitis where viral clearance depends on the local actions of anti-viral antibodies, CXCL13 levels and B cell numbers increased in brain tissue over time. Surprisingly, however, CXCL13-deficient animals showed normal CNS B cell recruitment, unaltered CNS virus replication and clearance, and intact peripheral anti-viral antibody responses. During experimental autoimmune encephalomyelitis (EAE), CNS levels of CXCL13 increased as symptoms emerged and equivalent numbers of B cells were identified among the CNS infiltrates of CXCL13-deficient mice compared to control animals. However, CXCL13-deficient mice did not sustain pathogenic anti-myelin T cell responses, consistent with their known propensity to develop more self-limited EAE. These data show that CXCL13 is dispensable for CNS B cell recruitment in both models. The disease course is unaffected by CXCL13 in a CNS infection paradigm that depends on a pathogen-specific B cell response, while it is heightened and prolonged by CXCL13 when myelin-specific CD4+ T cells drive CNS pathology. Thus, CXCL13 could be a therapeutic target in certain neuroinflammatory diseases, but not by blocking B cell recruitment to the CNS.
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影响因子：
3.3
作者：
Columba-Cabezas, Sandra;Griguoli, Marilena;Aloisi, Francesca
通讯作者：
Aloisi, Francesca
影响因子：
20.3
作者：
Carson, Kenneth R.;Evens, Andrew M.;Bennett, Charles L.
通讯作者：
Bennett, Charles L.
影响因子：
6
作者：
Ljostad, Unn;Mygland, Ase
通讯作者：
Mygland, Ase
DOI：
10.1056/nejmoa0706383
发表时间：
2008-02-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hauser, Stephen L;Waubant, Emmanuelle;Smith, Craig H
通讯作者：
Smith, Craig H
影响因子：
64.8
作者：
Ansel, KM;Ngo, VN;Cyster, JG
通讯作者：
Cyster, JG