Su G H, Chen H M, Muthusamy N, Garrett-Sinha L A, Baunoch D, Tenen D G, Simon M C
Committee on Immunology, University of Chicago, Chicago IL 60637, USA.
EMBO J. 1997 Dec 1;16(23):7118-29. doi: 10.1093/emboj/16.23.7118.
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 IgG1, IgG2a and IgG2b 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.
Spi-B是一种造血特异性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。我们现已培育出Spi-B基因座发生无效突变的小鼠。与PU.1突变小鼠不同，Spi-B基因敲除小鼠能够存活、繁殖，并且拥有成熟的B淋巴细胞和T淋巴细胞。然而，Spi-B基因敲除小鼠在B细胞功能和选择性T细胞依赖性体液免疫反应方面表现出严重异常。首先，尽管Spi-B基因敲除小鼠的脾脏B细胞在体外对脂多糖刺激反应正常，但这些B细胞在受到B细胞受体（表面IgM）交联刺激时增殖能力差且死亡。其次，Spi-B基因敲除小鼠在体内表现出异常的T细胞依赖性抗原反应，免疫后产生低水平的抗原特异性IgG1、IgG2a和IgG2b。最后，Spi-B基因敲除小鼠在生发中心的形成和维持方面存在显著缺陷。与野生型动物相比，Spi-B基因敲除小鼠的生发中心更小且寿命短，凋亡B细胞数量显著增加。综上所述，这些结果表明Spi-B对于B细胞的抗原依赖性扩增、T细胞依赖性免疫反应以及体内正常生发中心的成熟至关重要。
