Rodriguez M, Kenny J J, Thiemann R L, Woloschak G E
Department of Neurology and Immunology, Mayo Medical School, Rochester, MN 55905.
Microb Pathog. 1990 Jan;8(1):23-35. doi: 10.1016/0882-4010(90)90005-b.
Intracerebral infection with Theiler's murine encephalomyelitis virus produces chronic immune-mediated demyelination in susceptible strains of mice. We examined the role of Ig in the pathogenesis of demyelination. In susceptible SJL/J mice (H-2s), suppression of B cell responses with IgG fraction of goat anti-mu (anti-mu IgG) from birth resulted in increased numbers and severity of demyelinating lesions in the spinal cord 35 days after infection. In contrast, treatment of resistant C57BL/10 (H-2b), C57BL/6 (H-2b), or B10.D2 (H-2d) mice with anti-mu IgG had no apparent effect since these mice did not develop demyelination or inflammation in the spinal cord following infection. Similar results were obtained with certain strains of B-cell deficient mice that exhibit the xid gene mutation. Male CBA/NJ (xid) showed increased meningeal inflammation and demyelination compared to male CBA/J mice. However, B6.CBAN, C3.CBAN, or C.CBAn mice showed no or minimal evidence of demyelination despite the presence of the xid mutation. In the SJL/J mouse, the majority of the humoral immune response to virus antigen was restricted to the IgG2b and IgM isotypes. These data indirectly support the hypothesis that immunoglobulins protect partially against development of virus-induced demyelination in susceptible but not resistant animals. In addition, the data argue strongly against the hypothesis that TMEV-induced demyelination is mediated predominantly by humoral autoimmune or humoral viral immune mechanisms.
用泰勒氏鼠脑脊髓炎病毒进行脑内感染会在易感品系小鼠中引发慢性免疫介导的脱髓鞘病变。我们研究了免疫球蛋白（Ig）在脱髓鞘病变发病机制中的作用。在易感的SJL/J小鼠（H-2s）中，从出生起用山羊抗μ链IgG组分（抗μIgG）抑制B细胞反应，会导致感染后35天脊髓中脱髓鞘病变的数量增加且严重程度加重。相比之下，用抗μIgG处理抗性的C57BL/10（H-2b）、C57BL/6（H-2b）或B10.D2（H-2d）小鼠没有明显效果，因为这些小鼠在感染后脊髓中未出现脱髓鞘或炎症。在某些表现出xid基因突变的B细胞缺陷小鼠品系中也得到了类似结果。雄性CBA/NJ（xid）小鼠与雄性CBA/J小鼠相比，脑膜炎症和脱髓鞘程度增加。然而，B6.CBAN、C3.CBAN或C.CBAn小鼠尽管存在xid突变，但未显示或仅有极少的脱髓鞘证据。在SJL/J小鼠中，对病毒抗原的大多数体液免疫反应局限于IgG2b和IgM同种型。这些数据间接支持了这样的假说，即免疫球蛋白在易感但非抗性动物中能部分保护机体抵抗病毒诱导的脱髓鞘病变的发展。此外，这些数据有力地反驳了泰勒氏鼠脑脊髓炎病毒诱导的脱髓鞘主要由体液自身免疫或体液病毒免疫机制介导的假说。
