Gavin Amanda L, Aït-Azzouzene Djemel, Ware Carl F, Nemazee David
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Biol Chem. 2003 Oct 3;278(40):38220-8. doi: 10.1074/jbc.M306852200. Epub 2003 Jul 16.
The tumor necrosis family member BAFF is limiting for the survival of follicular B lymphocytes, but excessive BAFF signaling can lead to autoimmunity, suggesting that its activity must be tightly regulated. We have identified a conserved alternate splice isoform of BAFF, called deltaBAFF, which lacks 57 nt encoding the A-A1 loop and is co-expressed with BAFF in many mouse and human myeloid cells. Mouse deltaBAFF appears on the plasma membrane, but unlike BAFF it is inefficiently released by proteolysis. DeltaBAFF can associate with BAFF in heteromultimers and diminish BAFF bioactivity and release. Thus, alternative splicing of the BAFF gene suppresses BAFF B cell stimulatory function in several ways, and deltaBAFF may promote other functions as well.
肿瘤坏死家族成员BAFF对滤泡B淋巴细胞的存活具有限制作用，但BAFF信号过度会导致自身免疫，这表明其活性必须受到严格调控。我们鉴定出一种BAFF的保守可变剪接异构体，称为δBAFF，它缺少编码A - A1环的57个核苷酸，并且在许多小鼠和人类髓系细胞中与BAFF共表达。小鼠δBAFF出现在质膜上，但与BAFF不同的是，它通过蛋白水解作用释放效率较低。δBAFF可以与BAFF形成异源多聚体，并降低BAFF的生物活性和释放。因此，BAFF基因的可变剪接通过多种方式抑制BAFF的B细胞刺激功能，并且δBAFF可能也促进其他功能。
