Department of Laboratory Medicine and Pathology, Center for Immunology, University of Minnesota, Minneapolis, MN 55414, USA.
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):716-21. doi: 10.1073/pnas.1013168108. Epub 2010 Dec 27.
The transcription factor Krüppel-like factor 2 (KLF2) is critical for normal trafficking of T lymphocytes, but its role in B cells is unclear. We report that B cell-specific KLF2 deficiency leads to decreased expression of the trafficking molecules CD62L and β7-integrin, yet expression of sphingosine-1 phosphate receptor 1 (which is a critical target of KLF2 in T cells) was, unexpectedly, minimally altered. Unexpectedly, Klf2 deletion led to a drastic reduction in the B1 B-cell pool and a substantial increase in transitional and marginal zone B-cell numbers. In addition, we observed that KLF2-deficient B cells showed increased apoptosis and impaired proliferation after B-cell receptor cross-linking. Gene expression analysis indicated that KLF2-deficient follicular B cells display numerous characteristics shared by normal marginal zone B cells, including reduced expression of several signaling molecules that may contribute to defective activation of these cells. Hence, our data indicate that KLF2 plays a critical role in dictating normal subset differentiation and functional reactivity of mature B cells.
转录因子 Krüppel 样因子 2（KLF2）对于 T 淋巴细胞的正常运输至关重要，但它在 B 细胞中的作用尚不清楚。我们报告称，B 细胞特异性的 KLF2 缺失会导致运输分子 CD62L 和 β7-整合素的表达减少，然而，出乎意料的是，鞘氨醇-1-磷酸受体 1（这是 T 细胞中 KLF2 的关键靶标）的表达几乎没有改变。出乎意料的是，Klf2 缺失导致 B1 B 细胞池明显减少，过渡区和边缘区 B 细胞数量显著增加。此外，我们观察到 KLF2 缺陷 B 细胞在 B 细胞受体交联后表现出凋亡增加和增殖受损。基因表达分析表明，KLF2 缺陷滤泡 B 细胞表现出许多与正常边缘区 B 细胞共有的特征，包括几种信号分子的表达降低，这可能导致这些细胞的激活缺陷。因此，我们的数据表明 KLF2 在决定成熟 B 细胞的正常亚群分化和功能反应性方面发挥着关键作用。
