Grant K R, Harnett W, Milligan G, Harnett M M
Department of Immunology, University of Strathclyde, Glasgow, UK.
Immunology. 1997 Apr;90(4):564-71. doi: 10.1046/j.1365-2567.1997.00196.x.
The molecular mechanisms underlying B- and T-cell development are, as yet, poorly understood. However, as G proteins regulate a diverse range of biological responses including growth, proliferation and differentiation, we have investigated differential expression of G proteins during B- and T-cell development with the aim of identifying key signals involved in lymphocyte maturation. Differential expression of beta 1/2 and alpha-subunits of the Gs-, i- and q-families was found throughout lymphoid development. Most strikingly, G alpha i1 and G alpha i1 were very weakly, or not expressed in pre-, immature and mature B cells, thymocytes or mature T cells, but strongly induced in mature B-lymphoblastoid cell lines, some of which have been used as models of germinal centre B cells, suggesting that expression of these G proteins may correlate with the later stages of B-cell development. In contrast, G alpha 16 expression was highest in T cells and pre-B cells and progressively declined with B-cell maturation. These findings suggest that G proteins, and the signals they regulate, such as ion channels and/or adenylate cyclase (G alpha s/i) and phospholipase C (G beta gamma and G alpha 11/16) are differentially regulated in lymphoid cells in a maturation-and lineage-dependent manner.
B细胞和T细胞发育的分子机制目前仍知之甚少。然而,由于G蛋白可调节包括生长、增殖和分化在内的多种生物学反应,我们研究了B细胞和T细胞发育过程中G蛋白的差异表达,旨在确定参与淋巴细胞成熟的关键信号。在整个淋巴细胞发育过程中,发现Gs、Gi和Gq家族的β1/2和α亚基存在差异表达。最显著的是,Gαi1和Gαi1在pre-B细胞、未成熟和成熟B细胞、胸腺细胞或成熟T细胞中表达非常弱或不表达,但在成熟B淋巴母细胞系中强烈诱导表达,其中一些已被用作生发中心B细胞的模型,这表明这些G蛋白的表达可能与B细胞发育的后期阶段相关。相比之下,Gα16在T细胞和pre-B细胞中表达最高,并随着B细胞成熟而逐渐下降。这些发现表明,G蛋白及其调节的信号,如离子通道和/或腺苷酸环化酶(Gαs/i)以及磷脂酶C(Gβγ和Gα11/16)在淋巴细胞中以成熟和谱系依赖的方式受到差异调节。