Max Planck Institute of Immunobiology, Freiburg, Germany.
Blood. 2011 Apr 7;117(14):3780-92. doi: 10.1182/blood-2010-09-308742. Epub 2011 Feb 4.
Splenic marginal zone (MZ) B cells are a lineage distinct from follicular and peritoneal B1 B cells. They are located next to the marginal sinus where blood is released. Here they pick up antigens and shuttle the load onto follicular dendritic cells inside the follicle. On activation, MZ B cells rapidly differentiate into plasmablasts secreting antibodies, thereby mediating humoral immune responses against blood-borne type 2 T-independent antigens. As Krüppel-like factors are implicated in cell differentiation/function in various tissues, we studied the function of basic Krüppel-like factor (BKLF/KLF3) in B cells. Whereas B-cell development in the bone marrow of KLF3-transgenic mice was unaffected, MZ B-cell numbers in spleen were increased considerably. As revealed in chimeric mice, this occurred cell autonomously, increasing both MZ and peritoneal B1 B-cell subsets. Comparing KLF3-transgenic and nontransgenic follicular B cells by RNA-microarray revealed that KLF3 regulates a subset of genes that was similarly up-regulated/down-regulated on normal MZ B-cell differentiation. Indeed, KLF3 expression overcame the lack of MZ B cells caused by different genetic alterations, such as CD19-deficiency or blockade of B-cell activating factor-receptor signaling, indicating that KLF3 may complement alternative nuclear factor-κB signaling. Thus, KLF3 is a driving force toward MZ B-cell maturation.
脾脏边缘区 (MZ) B 细胞是一种与滤泡和腹膜 B1 B 细胞不同的谱系。它们位于边缘窦旁边，血液从这里释放。在那里，它们摄取抗原，并将负载转移到滤泡内的滤泡树突状细胞上。在激活时，MZ B 细胞迅速分化为浆母细胞，分泌抗体，从而介导针对血源 2 型 T 细胞非依赖性抗原的体液免疫反应。由于 Krüppel 样因子在各种组织的细胞分化/功能中起作用，我们研究了基本 Krüppel 样因子 (BKLF/KLF3) 在 B 细胞中的功能。尽管 KLF3 转基因小鼠的骨髓中 B 细胞发育不受影响，但脾脏中的 MZ B 细胞数量显著增加。嵌合小鼠研究表明，这种情况是细胞自主发生的，增加了 MZ 和腹膜 B1 B 细胞亚群。通过 RNA 微阵列比较 KLF3 转基因和非转基因滤泡 B 细胞，发现 KLF3 调节了一组基因，这些基因在正常 MZ B 细胞分化过程中同样被上调/下调。事实上，KLF3 的表达克服了不同遗传改变（如 CD19 缺陷或 B 细胞激活因子受体信号阻断）引起的 MZ B 细胞缺乏，表明 KLF3 可能补充替代核因子-κB 信号。因此，KLF3 是 MZ B 细胞成熟的驱动力。
