McCoy K L, Clagett J, Rosse C
Exp Hematol. 1985 Jul;13(6):554-9.
The rapidly fatal autoimmune disease in the mutant mouse known as motheaten is caused by an autosomal recessive gene and is characterized by hypergammaglobulinemia and autoantibody production, among other defects. The cellular kinetics of B-cell maturation were investigated in three-week-old motheaten mice and their normal littermates to determine whether any abnormality in cell production of the B lineage could be correlated with B-cell hyperactivity. The production rates and renewal times of newly produced bone marrow, splenic small B-lymphocytes, and splenic plasma cells were examined by in vivo tritiated-thymidine administration using a pulse-chase protocol and radioautography of immunofluorescence-stained cells. Because small B-lymphocytes in both organs were produced at comparable rates in the mutant mice and in their normal littermates, primary B-cell production was unaffected in the mutant mice. In contrast, splenic plasma cells were produced 10-30 times faster in motheaten mice than in normal mice. The enhanced rate of plasma cell production in motheaten mice could be correlated with a concurrent increased loss of labeled large B-lymphocytes, presumably rapidly dividing activated B cells. Thus, the excessive antibody production in motheaten mice may be reflected by the increased plasma cell production.
在被称为“脱毛”的突变小鼠中，这种迅速致命的自身免疫性疾病是由常染色体隐性基因引起的，其特征包括高丙种球蛋白血症和自身抗体产生等缺陷。对三周龄的“脱毛”小鼠及其正常同窝仔鼠的B细胞成熟的细胞动力学进行了研究，以确定B细胞谱系的细胞产生是否存在任何异常，以及这种异常是否与B细胞的过度活跃相关。通过使用脉冲追踪方案体内注射氚标记胸腺嘧啶核苷以及对免疫荧光染色细胞进行放射自显影，检测了新产生的骨髓、脾脏小B淋巴细胞和脾脏浆细胞的产生率和更新时间。由于突变小鼠及其正常同窝仔鼠中两个器官的小B淋巴细胞产生速率相当，因此突变小鼠的初级B细胞产生未受影响。相比之下，“脱毛”小鼠脾脏浆细胞的产生速度比正常小鼠快10到30倍。“脱毛”小鼠浆细胞产生速率的提高可能与标记的大B淋巴细胞同时增加的损失有关，推测这些大B淋巴细胞是快速分裂的活化B细胞。因此，“脱毛”小鼠中过量的抗体产生可能反映在浆细胞产生的增加上。
