Defective B cell receptor-mediated responses in mice lacking the Ets protein, Spi-B
Defective B cell receptor-mediated responses in mice lacking the Ets protein, Spi-B
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DOI：
10.1093/emboj/16.23.7118
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发表时间：
1997-12-01
期刊：
影响因子：
11.4
通讯作者：
Simon, MC
中科院分区：
文献类型：
--
作者：
Su, GH;Chen, HM;Simon, MC
Spi-B是造血特异性Ets家族转录因子，与PU.1密切相关。先前的基因靶向实验表明，PU.1 对于淋巴细胞和单核细胞的产生至关重要。我们现在已经生成了 Spi-B 基因座无突变的小鼠。与 PU.1 突变小鼠不同，Spi-B-/- 小鼠具有存活能力、生育能力并拥有成熟的 B 和 T 淋巴细胞。然而，Spi-B-/-小鼠的B细胞功能和选择性T细胞依赖性体液免疫反应表现出严重异常，首先，尽管Spi-B-/-脾B细胞在体外对脂多糖刺激反应正常，但这些B细胞增殖不良，并因B细胞受体（表面IgM）交联而死亡。其次，Spi-B-/-小鼠在体内表现出异常的T依赖性抗原反应，并在免疫后产生低水平的抗原特异性IgG(1)、IgG(2a)和IgG(2b)。最后，Spi-B-/- 小鼠在生发中心的形成和维持方面表现出显着的缺陷。与野生型动物相比，Spi-B-/-小鼠的生发中心更小、寿命更短，凋亡的 B 细胞数量显着增加。总而言之，这些结果表明 Spi-B 对于 B 细胞的抗原依赖性扩增、T 依赖性免疫反应和体内正常生发中心的成熟至关重要。
Spi-B is a hematopoietic-specific Ets family transcription factor closely related to PU.1. Previous gene targeting experiments have shown that PU.1 is essential for the production of both lymphocytes and monocytes. We have now generated mice with a null mutation at the Spi-B locus. Unlike PU.1 mutant mice, Spi-B-/- mice are viable, fertile and possess mature B and T lymphocytes. However, Spi-B-/- mice exhibit severe abnormalities in B cell function and selective T cell-dependent humoral immune responses, First, although Spi-B-/- splenic B cells respond normally to lipopolysaccharide stimulation in vitro, these B cells proliferate poorly and die in response to B cell receptor (surface IgM) cross-linking. Secondly, Spi-B-/- mice display abnormal T-dependent antigenic responses in vivo and produce low levels of antigen-specific IgG(1), IgG(2a) and IgG(2b) after immunization. Finally, Spi-B-/- mice show a dramatic defect in germinal center formation and maintenance. In contrast to wild-type animals, germinal centers in Spi-B-/- mice are smaller and short-lived with significantly increased numbers of apoptotic B cells, Taken together, these results demonstrate that Spi-B is essential for antigen-dependent expansion of B cells, T-dependent immune responses and maturation of normal germinal centers in vivo.