Mackay Fabienne, Ambrose Christine
Department of Arthritis and Inflammation, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2030, Australia.
Cytokine Growth Factor Rev. 2003 Jun-Aug;14(3-4):311-24. doi: 10.1016/s1359-6101(03)00023-6.
B cell activating factor belonging to the TNF family (BAFF) and apoptosis-inducing ligand (APRIL) are two related members of the TNF ligand superfamily. Although they share two receptors, TACI and BCMA, transgenic and knockout mice in this system reveal that their functions are not redundant. BAFF is a critical survival/maturation factor for peripheral B cells and this activity is mediated through a BAFF-specific receptor, BAFF-R. Overexpression of BAFF has been linked to autoimmune disease and aspects of B cell neoplasia. APRIL appears to play a role in T-independent type II antigen responses and T cell survival, but can also induce proliferation/survival of non-lymphoid cells. Elevated expression of APRIL has been found in some tumor cell lines and in tumor tissue libraries. Therapies designed to inhibit the BAFF and APRIL pathways holds great promise for the future.
肿瘤坏死因子家族的B细胞活化因子(BAFF)和凋亡诱导配体(APRIL)是肿瘤坏死因子配体超家族的两个相关成员。尽管它们共享两种受体,即跨膜激活剂和钙调素配体相互作用分子(TACI)和B细胞成熟抗原(BCMA),但该系统中的转基因和基因敲除小鼠显示它们的功能并非冗余。BAFF是外周B细胞关键的存活/成熟因子,且该活性通过一种BAFF特异性受体BAFF-R介导。BAFF的过表达与自身免疫性疾病和B细胞肿瘤形成的某些方面有关。APRIL似乎在II型非依赖T细胞抗原应答和T细胞存活中发挥作用,但也可诱导非淋巴细胞的增殖/存活。在一些肿瘤细胞系和肿瘤组织文库中发现了APRIL的表达升高。旨在抑制BAFF和APRIL途径的疗法在未来具有很大的前景。