Swanson-Mungerson Michelle, Bultema Rebecca, Longnecker Richard
Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Ward 6-231, 303 E. Chicago Ave., Chicago, IL 60611, USA.
J Virol. 2006 Jul;80(14):6764-70. doi: 10.1128/JVI.00433-06.
Epstein-Barr virus (EBV) establishes latent infections in a significant percentage of the population. Latent membrane protein 2A (LMP2A) is an EBV protein expressed during latency that inhibits B-cell receptor signaling in lymphoblastoid cell lines. In the present study, we have utilized a transgenic mouse system in which LMP2A is expressed in B cells that are specific for hen egg lysozyme (E/HEL-Tg). To determine if LMP2A allows B cells to respond to antigen, E/HEL-Tg mice were immunized with hen egg lysozyme. E/HEL-Tg mice produced antibody in response to antigen, indicating that LMP2A allows B cells to respond to antigen. In addition, E/HEL-Tg mice produced more antibody and an increased percentage of plasma cells after immunization compared to HEL-Tg littermates, suggesting that LMP2A increased the antibody response in vivo. Finally, in vitro studies determined that LMP2A acts directly on the B cell to increase antibody production by augmenting the expansion and survival of the activated B cells, as well as increasing the percentage of plasma cells generated. Taken together, these data suggest that LMP2A enhances, not diminishes, B-cell-specific antibody responses in vivo and in vitro in the E/HEL-Tg system.
爱泼斯坦-巴尔病毒（EBV）在相当比例的人群中建立潜伏感染。潜伏膜蛋白2A（LMP2A）是一种在潜伏期表达的EBV蛋白，可抑制淋巴母细胞系中的B细胞受体信号传导。在本研究中，我们利用了一种转基因小鼠系统，其中LMP2A在对鸡卵溶菌酶特异的B细胞中表达（E/HEL-Tg）。为了确定LMP2A是否使B细胞能够对抗原作出反应，用鸡卵溶菌酶对E/HEL-Tg小鼠进行免疫。E/HEL-Tg小鼠对抗原产生抗体反应，表明LMP2A使B细胞能够对抗原作出反应。此外，与HEL-Tg同窝小鼠相比，E/HEL-Tg小鼠在免疫后产生更多抗体且浆细胞百分比增加，这表明LMP2A在体内增强了抗体反应。最后，体外研究确定LMP2A直接作用于B细胞，通过增强活化B细胞的扩增和存活以及增加产生的浆细胞百分比来增加抗体产生。综上所述，这些数据表明在E/HEL-Tg系统中，LMP2A在体内和体外增强而非减弱B细胞特异性抗体反应。
