Ramakrishna Chandran, Stohlman Stephen A, Atkinson Roscoe D, Shlomchik Mark J, Bergmann Cornelia C
Department of Neurology, Keck School of Medicine, University of Southern California, 1333 San Pablo Street, Los Angeles, CA 90033, USA.
J Immunol. 2002 Feb 1;168(3):1204-11. doi: 10.4049/jimmunol.168.3.1204.
Contributions of humoral and cellular immunity in controlling neurotropic mouse hepatitis virus persistence within the CNS were determined in B cell-deficient J(H)D and syngeneic H-2(d) B cell+ Ab-deficient mice. Virus clearance followed similar kinetics in all mice, confirming initial control of virus replication by cellular immunity. Nevertheless, virus reemerged within the CNS of all Ab-deficient mice. In contrast to diminished T cell responses in H-2(b) B cell-deficient muMT mice, the absence of B cells or Ab in the H-2(d) mice did not compromise expansion, recruitment into the CNS, or function of virus-specific CD4+ and CD8+ T cells. The lack of B cells and lymphoid architecture thus appears to manifest itself on T cell responses in a genetically biased manner. Increasing viral load did not enhance frequencies or effector function of virus-specific T cells within the CNS, indicating down-regulation of T cell responses. Although an Ab-independent antiviral function of B cells was not evident during acute infection, the presence of B cells altered CNS cellular tropism during viral recrudescence. Reemerging virus localized almost exclusively to oligodendroglia in B cell+ Ab-deficient mice, whereas it also replicated in astrocytes in B cell-deficient mice. Altered tropism coincided with distinct regulation of CNS virus-specific CD4+ T cells. These data conclusively demonstrate that the Ab component of humoral immunity is critical in preventing virus reactivation within CNS glial cells. B cells themselves may also play a subtle role in modulating pathogenesis by influencing tropism.
在B细胞缺陷的J(H)D小鼠和同基因H-2(d) B细胞+抗体缺陷小鼠中，确定了体液免疫和细胞免疫在控制嗜神经小鼠肝炎病毒在中枢神经系统内持续存在方面的作用。所有小鼠的病毒清除遵循相似的动力学，证实了细胞免疫对病毒复制的初始控制。然而，病毒在所有抗体缺陷小鼠的中枢神经系统内重新出现。与H-2(b) B细胞缺陷的muMT小鼠中T细胞反应减弱不同，H-2(d)小鼠中B细胞或抗体的缺失并未损害病毒特异性CD4+和CD8+ T细胞的扩增、向中枢神经系统的募集或功能。因此，B细胞和淋巴组织结构的缺失似乎以基因偏向的方式在T细胞反应中表现出来。病毒载量的增加并未增强中枢神经系统内病毒特异性T细胞的频率或效应功能，表明T细胞反应下调。虽然在急性感染期间B细胞的非抗体依赖性抗病毒功能不明显，但B细胞的存在在病毒复发期间改变了中枢神经系统的细胞嗜性。重新出现的病毒几乎完全定位于B细胞+抗体缺陷小鼠的少突胶质细胞，而在B细胞缺陷小鼠中它也在星形胶质细胞中复制。嗜性改变与中枢神经系统病毒特异性CD4+ T细胞的不同调节相吻合。这些数据确凿地证明，体液免疫的抗体成分对于防止病毒在中枢神经系统神经胶质细胞内重新激活至关重要。B细胞本身也可能通过影响嗜性在调节发病机制中发挥微妙作用。
