Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes.
Downregulated expression of SHP-1 in Burkitt lymphomas and germinal center B lymphocytes.
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DOI：
10.1084/jem.186.9.1575
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发表时间：
1997-11-03
期刊：
影响因子：
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通讯作者：
Fearon DT
中科院分区：
文献类型：
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作者：
Delibrias CC;Floettmann JE;Rowe M;Fearon DT
我们希望确定可能有助于其快速生长的生发中心B细胞的发育变化。SHP-1是一种含有SH 2结构域的磷酸酪氨酸磷酸酶，其负调节B细胞和造血谱系的其它细胞的活化。我们发现，在所有13个EBV阴性和11个EBV阳性的Burkitt淋巴瘤与非淋巴母细胞样表型，SHP-1的平均浓度降低到5%的正常B和T细胞。SHP-1表达的减少与伯基特淋巴瘤的生发中心表型有关的可能性得到生发中心SHP-1免疫荧光染色的低至缺失以及SHP-1浓度与纯化的扁桃体B细胞上生发中心标志物CD 38表达之间的负相关性的支持。在CD 38-高B细胞中，SHP-1浓度是来自同一供体的套带B细胞的20%。SHP-1的这种减少与来自受蛾存活的mev/mev小鼠的细胞的减少相当，其中存在由细胞因子和抗原受体引起的失调的自发信号传导。因此，生发中心B细胞可能具有发育调节的低细胞活化阈值。
We wish to identify developmental changes in germinal center B cells that may contribute to their rapid growth. SHP-1 is an SH2 domain–containing phosphotyrosine phosphatase that negatively regulates activation of B cells and other cells of hematopoietic lineages. We have found that in all 13 EBV-negative and 11 EBV-positive Burkitt lymphomas with a nonlymphoblastoid phenotype, the mean concentration of SHP-1 was reduced to 5% of that of normal B and T cells. The possibility that this diminished expression of SHP-1 was related to the germinal center phenotype of Burkitt lymphomas was supported by the low to absent immunofluorescent staining for SHP-1 in germinal centers, and by the inverse relationship between the concentration of SHP-1 and the expression of the germinal center marker CD38 on purified tonsillar B cells. In CD38-high B cells, SHP-1 concentration was 20% of that of mantle zone B cells from the same donor. This reduction in SHP-1 is comparable to that of cells from motheaten viable mev/mev mice in which there is dysregulated, spontaneous signaling by cytokine and antigen receptors. Therefore, germinal center B cells may have a developmentally regulated, low threshold for cellular activation.