Nagumo Haruo, Abe Jun, Kano Hirotsugu, Taki Shinsuke, Yamazaki Kazuko, Yamazaki Takashi, Kobayashi Norimoto, Koike Kenichi, Sugane Kazuo, Saito Hirohisa, Agematsu Kazunaga
Department of Infection and Host Defense, Shinshu University, Asahi, Matsumoto, Nagano, Japan.
Cell Immunol. 2009;256(1-2):56-63. doi: 10.1016/j.cellimm.2009.01.005. Epub 2009 Feb 23.
The molecular mechanisms involving in B-cell survival/proliferation are poorly understood. Here we investigated the molecules affecting the survival of human naïve and memory B cells. Without stimulation, naïve B cells survived longer than memory B cells. Moreover, the viability of memory B cells decreased more rapidly than that of naïve B cells following with Staphylococcus aureus Cowan strain (SAC), anti-immunoglobulin (Ig), or anti-CD40 stimulation, but displayed the same levels of survival following CpG DNA stimulation. We analyzed the transcriptional differences between B-cell subsets by gene expression profiling, and identified 15 genes significantly correlated to survival/proliferation. Among them, IL-21 receptor (IL-21R) and T-cell leukemia 1 (TCL1) proto-oncogene were highly expressed in naïve B cells. IL-21 induced the proliferation of both naïve and memory B cells. Marked phosphorylation of Akt was found in naïve B cells compared with memory B cells. This study suggests that naive and memory B cells are regulated by several distinct molecules, and the IL-21R and TCL1/Akt pathways might play crucial roles in naïve B cells for their maintenance.
目前对参与B细胞存活/增殖的分子机制了解甚少。在此，我们研究了影响人类初始B细胞和记忆B细胞存活的分子。在无刺激情况下，初始B细胞比记忆B细胞存活时间更长。此外，在用金黄色葡萄球菌考恩株（SAC）、抗免疫球蛋白（Ig）或抗CD40刺激后，记忆B细胞的活力比初始B细胞下降得更快，但在CpG DNA刺激后显示出相同的存活水平。我们通过基因表达谱分析了B细胞亚群之间的转录差异，并鉴定出15个与存活/增殖显著相关的基因。其中，白细胞介素-21受体（IL-21R）和T细胞白血病1（TCL1）原癌基因在初始B细胞中高表达。IL-21可诱导初始B细胞和记忆B细胞的增殖。与记忆B细胞相比，在初始B细胞中发现了明显的Akt磷酸化。这项研究表明，初始B细胞和记忆B细胞受几种不同分子的调控，并且IL-21R和TCL1/Akt途径可能在初始B细胞的维持中起关键作用。
