School of Molecular Bioscience, University of Sydney, Sydney, New South Wales 2006, Australia.
J Immunol. 2011 Nov 15;187(10):5032-42. doi: 10.4049/jimmunol.1101450. Epub 2011 Oct 14.
Krüppel-like factor 3 (Klf3) is a member of the Klf family of transcription factors. Klfs are widely expressed and have diverse roles in development and differentiation. In this study, we examine the function of Klf3 in B cell development by studying B lymphopoiesis in a Klf3 knockout mouse model. We show that B cell differentiation is significantly impaired in the bone marrow, spleen, and peritoneal cavity of Klf3 null mice and confirm that the defects are cell autonomous. In the bone marrow, there is a reduction in immature B cells, whereas recirculating mature cells are noticeably increased. Immunohistology of the spleen reveals a poorly structured marginal zone (MZ) that may in part be caused by deregulation of adhesion molecules on MZ B cells. In the peritoneal cavity, there are significant defects in B1 B cell development. We also report that the loss of Klf3 in MZ B cells is associated with reduced BCR signaling strength and an impaired ability to respond to LPS stimulation. Finally, we show increased expression of a number of Klf genes in Klf3 null B cells, suggesting that a Klf regulatory network may exist in B cells.
Krüppel 样因子 3（Klf3）是 Klf 转录因子家族的成员之一。Klf 在发育和分化过程中广泛表达，具有多种功能。在这项研究中，我们通过研究 Klf3 敲除小鼠模型中的 B 细胞发生，来研究 Klf3 在 B 细胞发育中的功能。我们发现 Klf3 缺失小鼠的骨髓、脾脏和腹腔中的 B 细胞分化受到严重损害，并且证实这些缺陷是细胞自主性的。在骨髓中，未成熟 B 细胞减少，而循环成熟细胞明显增加。脾脏的免疫组织化学分析显示，边缘区（MZ）结构不良，这可能部分是由于 MZ B 细胞上黏附分子的失调所致。在腹腔中，B1 B 细胞的发育存在显著缺陷。我们还报告称，MZ B 细胞中 Klf3 的缺失与 BCR 信号强度降低以及对 LPS 刺激的反应能力受损有关。最后，我们发现 Klf3 缺失 B 细胞中许多 Klf 基因的表达增加，这表明 B 细胞中可能存在 Klf 调控网络。
