Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T
Department of Medical Chemistry, Graduate School of Medicine, Institute for Virus Research, Kyoto University, Japan.
Cell. 2000 Sep 1;102(5):553-63. doi: 10.1016/s0092-8674(00)00078-7.
Induced overexpression of AID in CH12F3-2 B lymphoma cells augmented class switching from IgM to IgA without cytokine stimulation. AID deficiency caused a complete defect in class switching and showed a hyper-IgM phenotype with enlarged germinal centers containing strongly activated B cells before or after immunization. AID-/- spleen cells stimulated in vitro with LPS and cytokines failed to undergo class switch recombination although they expressed germline transcripts. Immunization of AID-/- chimera with 4-hydroxy-3-nitrophenylacetyl (NP) chicken gamma-globulin induced neither accumulation of mutations in the NP-specific variable region gene nor class switching. These results suggest that AID may be involved in regulation or catalysis of the DNA modification step of both class switching and somatic hypermutation.
在CH12F3-2 B淋巴瘤细胞中诱导AID过表达，可在无细胞因子刺激的情况下增强从IgM到IgA的类别转换。AID缺陷导致类别转换完全缺陷，并表现出高IgM表型，生发中心在免疫前后均增大，含有强烈活化的B细胞。用LPS和细胞因子体外刺激的AID-/-脾细胞尽管表达了种系转录本，但仍未能进行类别转换重组。用4-羟基-3-硝基苯乙酰（NP）鸡γ球蛋白免疫AID-/-嵌合体，既未诱导NP特异性可变区基因中的突变积累，也未发生类别转换。这些结果表明，AID可能参与类别转换和体细胞超突变的DNA修饰步骤的调控或催化。
