Dang A M, Phillips J A, Lin T, Raveche E S
Department of Pathology, UMDNJ/New Jersey Medical School, Newark 07103, USA.
Cell Immunol. 1996 May 1;169(2):196-207. doi: 10.1006/cimm.1996.0110.
CD45 is an important surface glycoprotein which has an intrinsic tyrosine phosphatase activity and has been implicated in cell proliferation, signaling, and differentiation and is associated with the B cell receptor during signaling. In this manuscript, the role of CD45 expression in the development of B-1 malignancies in NZB mice, which serve as a model for human diseases such as chronic lymphocytic leukemia, was investigated. B-1 cells spontaneously hyperproliferate and form a clonal hyperdiploid malignant population in aging NZB mice. Phenotypic analysis indicates that the NZB malignant B-1 cells are bright for IgM, but have reduced levels of CD45 relative to normal, nonmalignant B cells (both B-1 and B-2) and are characterized by dull or negative expression of the CD45 isoform B220/6B2 normally found on all B cells. Malignant B-1 cells demonstrated decreased RNA levels of CD45 relative to IgM expression, while nonmalignant B-2 cells showed similar levels of RNA expression for both CD45 and IgM. As CD45 exists in several isoforms and B cells express the highest molecular weight isoform (B220), malignant B-1 cells were further analyzed with respect to their isoform usage. Although, at the RNA level malignant B-1 cells showed the presence of the of the B220 form of CD45, western blot analysis of B220 protein suggested a posttranslational glycosylation defect in the CD45/B220 expression recognized by the mAb 6B2. F1 recipients of premalignant NZB B-1 cells which had been sorted for IgMhi, B220/6B2negative cells developed hyperdiploid malignant donor B-1 clones earlier than did recipients of NZB B-1 cells which were bright for B220/6B2. However, all the malignant B-1 clones of NZB origin which developed in recipients of both transfer populations were B220/6B2 negative. This indicated that abnormal expression of CD45 may be prerequisite for long-term growth and malignant transformation. Thus alterations in CD45 may result in abnormal functioning of the malignant B-1 cells which may further affect the proliferation of, or signaling within, these cells.
CD45是一种重要的表面糖蛋白，具有内在的酪氨酸磷酸酶活性，与细胞增殖、信号传导和分化有关，并且在信号传导过程中与B细胞受体相关。在本论文中，研究了CD45表达在NZB小鼠B-1恶性肿瘤发生发展中的作用，NZB小鼠可作为人类疾病如慢性淋巴细胞白血病的模型。在衰老的NZB小鼠中，B-1细胞自发过度增殖并形成克隆性超二倍体恶性群体。表型分析表明，NZB恶性B-1细胞的IgM呈明亮表达，但相对于正常的非恶性B细胞（B-1和B-2），其CD45水平降低，其特征是通常在所有B细胞上发现的CD45同种型B220/6B2呈暗淡或阴性表达。与IgM表达相比，恶性B-1细胞的CD45 RNA水平降低，而非恶性B-2细胞的CD45和IgM RNA表达水平相似。由于CD45存在多种同种型，且B细胞表达分子量最高的同种型（B220），因此对恶性B-1细胞的同种型使用情况进行了进一步分析。虽然在RNA水平上，恶性B-1细胞显示存在CD45的B220形式，但对B220蛋白的蛋白质印迹分析表明，单克隆抗体6B2识别的CD45/B220表达存在翻译后糖基化缺陷。对IgM高、B220/6B2阴性的NZB前恶性B-1细胞进行分选，其F1受体比B220/6B2呈明亮表达的NZB B-1细胞受体更早地产生超二倍体恶性供体B-1克隆。然而，在两个转移群体的受体中产生的所有NZB来源的恶性B-1克隆均为B220/6B2阴性。这表明CD45的异常表达可能是长期生长和恶性转化的先决条件。因此，CD45的改变可能导致恶性B-1细胞功能异常，进而可能进一步影响这些细胞的增殖或信号传导。
