Recruitment kinetics and composition of antibody-secreting cells within the central nervous system following viral encephalomyelitis
Recruitment kinetics and composition of antibody-secreting cells within the central nervous system following viral encephalomyelitis
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DOI：
10.4049/jimmunol.168.6.2922
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发表时间：
2002-03-15
影响因子：
4.4
通讯作者：
Stohlman, SA
中科院分区：
文献类型：
--
作者：
Tschen, SI;Bergmann, CC;Stohlman, SA
小鼠肝炎病毒嗜神经性JHM株感染可引起急性脱髓鞘性脑脊髓炎。虽然细胞免疫最初消除感染性病毒，但CNS病毒持续存在主要由体液免疫控制。为了更好地理解CNS内免疫控制的不同阶段，在感染小鼠中测定体液免疫应答的动力学。在小鼠肝炎病毒JHM株清除的早期，在外周或CNS中仅检测到少数病毒特异性Absecreting细胞（ASC），尽管成熟的B细胞和无病毒特异性的ASC与T细胞一起被募集到CNS中。血清抗病毒抗体和中枢神经系统病毒特异性ASC仅在感染性病毒最终消除期间才变得突出。病毒特异性ASC在CNS之前的淋巴器官中达到峰值，表明外周B细胞启动和成熟。在消除感染性病毒后，病毒特异性ASC在CNS内继续增加，然后在持续期间保持稳定，与T细胞数量下降相反。这些数据包括三个新的发现。在不存在特异性Ab分泌的情况下快速募集B细胞支持涉及病毒感染细胞裂解的潜在Ab非依赖性效应子功能。相对于病毒清除的延迟募集和随后稳定的CNS ASC群体的维持证明了感染的CNS内T和B淋巴细胞的差异调节。这支持了体液免疫在调节病毒CNS持久性中的关键作用。最后，感染性病毒清除后抗病毒ASC特异性的改变表明外周记忆细胞和/或局部B细胞分化的持续募集。
Infection by the neurotropic JHM strain of mouse hepatitis virus produces an acute demyelinating encephalomyelitis. While cellular immunity initially eliminates infectious virus, CNS viral persistence is predominantly controlled by humoral immunity. To better understand the distinct phases of immune control within the CNS, the kinetics of humoral immune responses were determined in infected mice. Early during clearance of the JHM strain of mouse hepatitis virus, only few virus-specific Absecreting cells (ASC) were detected in the periphery or CNS, although mature B cells and ASC without viral specificity were recruited into the CNS concomitant with T cells. Serum antiviral Ab and CNS virus-specific ASC became prominent only during final elimination of infectious virus. Virus-specific ASC peaked in lymphoid organs before the CNS, suggesting peripheral B cell priming and maturation. Following elimination of infectious virus, virus-specific ASC continued to increase within the CNS and then remained stable during persistence, in contrast to declining T cell numbers. These data comprise three novel findings. Rapid recruitment of B cells in the absence of specific Ab secretion supports a potential Ab-independent effector function involving lysis of virus-infected cells. Delayed recruitment relative to viral clearance and subsequent maintenance of a stable CNS ASC population demonstrate differential regulation of T and B lymphocytes within the infected CNS. This supports a critical role of humoral immunity in regulating viral CNS persistence. Lastly, altered antiviral ASC specificities following clearance of infectious virus suggest ongoing recruitment of peripheral memory cells and/or local B cell differentiation.