Regulation of the Expression of CD45 alternative Structures in Lymphocyte Subsets

CD45是一个膜整合蛋白酪氨酸磷酸酶家族，被认为参与了淋巴细胞信号转导的调节。CD45分子的外膜结构域有3种选择性结构，外显子4、5和6的选择性剪接产生了8种异构体。我们分析了小鼠CD45树状替代结构(CD45RA、B和C)的差异表达与淋巴细胞亚群的个体发育和分化的关系。结果如下：外周B细胞均为CD45RA+B+C+，但这些表位在骨髓B系细胞上的表达存在差异。尽管前B细胞早期开始表达三种不同的CD45表位，但每个表位的表达过程不同，CD45RA和CD45RC的表达几乎一致，而CD45RB的表达明显延迟。由于所有三种可供选择的CD45mRNA表达都发生在前B细胞的早期阶段，并且前…在随后的发育阶段，CD45RB表达的延迟似乎是由于翻译后事件导致的：脾中的CD4+T细胞包括两个群体，CD45RA-B+C-和CD45RA-B+C+。在这些细胞中，交替外显子的信息与CD45转录的骨(外显子4或外显子5)或两个外显子形式(外显子5和外显子6)相关联。当固定化CD3单抗刺激CD45RC+CD4+T细胞时，CD45RC+CD4+T细胞分泌IL-2，而不分泌其他细胞因子，如IL-4、干扰素-g或IL-10，从而代表“幼稚”的THP类型细胞。CD8+T细胞：脾CD8+T细胞分为CD45RA-B+C+和CD45RA+B+C+。有一个、两个或三个可选外显子的转录本表明，这些细胞表达不同类型的CD45亚型，包括具有所有三个可选结构的最大形式。对体外建立的T细胞克隆的研究表明，细胞毒CD8+T细胞克隆为CD45RA+，抑制效应CD8+T细胞克隆为CD45RA-。CD45RA-CD8+T细胞与CD45RA+CD8+T细胞功能差异的进一步研究正在进行中。较少

CD45 is a family of membrane-integral protein tyrosine phosphatase thought to be involved in the regulation of signal transduction in lymphocyte. Outer-membrane domain of the molecule has three alternative structures, and eight isoforms are generated by the alternative splicing of exons 4,5 and 6. We analyzed the differential expression of tree CD45 alternative structures (CD45RA,B and C) of mouse CD45 in relation to the ontogeny and differentiation of lymphocyte subsets. The results are summarized as followsB cells : While peripheral B cells were all CD45RA+B+C+, there were differential expressions of these epitopes on bone marrow B lineage cells. Although three alternative CD 45 epitopes began to be expressed at an early stage of pre B cells, the process of each epitope expression differed ; while the expression of CD45RA and CD45RC nearly coincided, CD45RB expression was markedly delayd. Since all three alternative CD45 mRNA expressions occurred at an early pre B cell stage, and pro … More gressively elevated in subsequent developmental stages, the observed delay in the CD45RB expression appeared to be due to post-translational eventsCD4+ T cells : Splenic CD4+ T cells included two populations, CD45RA-B+C- and CD45RA-B+C+. In these cells, messages of alternative exons were associated with either Bone (exon 4 or exon 5) or two exon form (exon 5 and exon 6) of the CD45 transcript.When stimulated by an immobilized CD3 mAb, the CD45RC+CD4+ T cells secreted IL-2 but not other cytokines such as IL-4, IFN-g or IL-10, thereby represented "naive" ThP-type cells. CD45RC-CD4+ T cells produced IL-2, IL-4, IFN-g and IL-10 and likely included both Th1- and Th2-type cells.CD8+ T cells : Splenic CD8+ T cells were separated into CD45RA-B+C+ and CD45RA+B+C+. There were transcripts with one, two, or three alternative exons suggesting that these cells express various types of CD45 isoforms including the largest form with all three alternative structures. Studies on T cell clones established in vitro revealed that while cytotoxic CD8+ T cells clones were CD45RA+, suppressor effecter CD8+ T cell clones were CD45RA-. Further studies on the functional difference between CD45RA-CD8+ T cells and CD45RA+CD8+ T cells are in progress. Less