Analysis of the fine B cell specificity during the chronic/relapsing course of a multiple sclerosis-like disease in Lewis rats injected with the encephalitogenic myelin oligodendrocyte glycoprotein peptide 35-55.
Analysis of the fine B cell specificity during the chronic/relapsing course of a multiple sclerosis-like disease in Lewis rats injected with the encephalitogenic myelin oligodendrocyte glycoprotein peptide 35-55.
复制标题
在注射致脑炎髓磷脂少突胶质细胞糖蛋白肽 35-55 的 Lewis 大鼠中，分析多发性硬化症样疾病慢性/复发过程中精细 B 细胞特异性。
DOI：
10.4049/jimmunol.157.2.919
复制
发表时间：
1996
影响因子：
4.4
通讯作者：
C. Bernard
中科院分区：
文献类型：
--
作者：
M. Ichikawa;T. Johns;J. Liu;C. Bernard
我们最近的研究表明，单次注射髓鞘少突胶质细胞糖蛋白（MOG）或MOG 35 -55肽，可产生一种复发缓解型神经系统疾病，伴有广泛的斑块样脱髓鞘。考虑到这种新的自身免疫性脱髓鞘模型与多发性硬化症的临床病理表现具有共同的特征，我们已经在刘易斯大鼠中检查了疾病过程中对天然MOG和MOG 35 -55肽的Ab反应性。MOG 35 -55免疫后，观察到不同的临床症状;其中包括后腿和前腿麻痹以及不同程度的平衡障碍。疾病进展也各不相同：21只动物中有3只发生了单次轻度疾病发作; 21只动物中有4只发生了轻度复发-缓解型疾病; 21只动物中有14只发生了重度复发-缓解型疾病。免疫后4周，在所有大鼠中首次检测到对MOG 35 -55和天然MOG的抗体反应性，并在整个12周的观察中持续存在。抗体反应是高度限制的，与其他肽，包括不同的细胞外片段的MOG没有反应性。精细表位作图显示，来自注射大鼠的血清和脑脊液的Ab对MOG 37 -46反应强烈，对MOG 43 -50反应程度较低。虽然抗MOG抗体的显着水平似乎是必要的脱髓鞘病变的发展，其存在于血液和脑脊液单独不足以产生严重的临床症状。这些结果证明MOG 35 -55肽是高度致脑炎的，并且可以诱导强的T和B细胞应答。可能正是这些T细胞和B细胞之间复杂的相互作用决定了个体大鼠疾病的严重程度。
We have recently shown that a single injection of myelin oligodendrocyte glycoprotein (MOG), or the MOG35-55 peptide, produces a relapsing-remitting neurologic disease with extensive plaque-like demyelination. Given the features that this new autoimmune demyelinating model has in common with the clinicopathologic manifestations of multiple sclerosis, we have examined the Ab reactivity to native MOG and MOG35-55 peptide during the course of the disease in Lewis rats. Following immunization with MOG35-55, varied clinical symptoms were observed; these included hind and foreleg paralysis and various degrees of balance impairment. Disease progression also varied: 3 out of 21 animals had a single mild disease episode; 4 out of 21 had a mild relapsing-remitting disease; and 14 out of 21 had severe relapsing-remitting disease. Ab reactivity to MOG35-55 and native MOG was first detected in all rats 4 wk postimmunization and persisted throughout the 12 wk of observation. The Ab response was highly restricted with no reactivity to other peptides encompassing different extracellular segments of MOG. Fine epitope mapping showed that Ab from serum and cerebrospinal fluid of injected rats reacted strongly to MOG37-46 and to a lesser extent to MOG43-50. Although significant levels of anti-MOG Abs appeared necessary for the development of demyelinating lesions, their presence in blood and cerebrospinal fluid alone was not sufficient to produce severe clinical symptoms. These results demonstrate that the MOG35-55 peptide is highly encephalitogenic and can induce strong T and B cell responses. It is probably the complex interaction between these T and B cells that determines the severity of disease in individual rats.