Martins Gislâine, Calame Kathryn
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
Annu Rev Immunol. 2008;26:133-69. doi: 10.1146/annurev.immunol.26.021607.090241.
B lymphocyte-induced maturation protein-1 (Blimp-1), discovered 16 years ago as a transcriptional repressor of the IFNbeta promoter, plays fundamentally important roles in many cell lineages and in early development. This review focuses on Blimp-1 in lymphocytes. In the B cell lineage, Blimp-1 is required for development of immunoglobulin-secreting cells and for maintenance of long-lived plasma cells (LLPCs). Direct targets of Blimp-1 and the transcriptional cascades Blimp-1 initiates to trigger plasmacytic differentiation are described. Blimp-1 also affects the homeostasis and function of CD4(+), CD8(+), and regulatory CD4(+) T cells, and Blimp-1 levels are highest in antigen-experienced T cells. Blimp-1 attenuates T cell proliferation and survival and modulates differentiation. Roles for Blimp-1 in Th1/Th2 specification, regulatory T cell function, and CD8 differentiation and function are under investigation. Signals that induce Blimp-1 in B cells include Toll-like receptor ligands and cytokines; in T cells, T cell receptors and cytokines induce Blimp-1. In spite of some commonalities, different targets and regulators of Blimp-1 in B and T cells suggest intriguing evolutionary divergence of this regulatory machinery.
B淋巴细胞诱导成熟蛋白-1(Blimp-1)于16年前作为IFNβ启动子的转录抑制因子被发现,在许多细胞谱系和早期发育中发挥着至关重要的作用。本综述聚焦于淋巴细胞中的Blimp-1。在B细胞谱系中,Blimp-1是免疫球蛋白分泌细胞发育和长寿浆细胞(LLPCs)维持所必需的。文中描述了Blimp-1的直接靶标以及Blimp-1启动的触发浆细胞分化的转录级联反应。Blimp-1还影响CD4⁺、CD8⁺和调节性CD4⁺ T细胞的稳态和功能,且在经历过抗原刺激的T细胞中Blimp-1水平最高。Blimp-1可减弱T细胞增殖和存活并调节分化。目前正在研究Blimp-1在Th1/Th2分化、调节性T细胞功能以及CD8分化和功能中的作用。在B细胞中诱导Blimp-1的信号包括Toll样受体配体和细胞因子;在T细胞中,T细胞受体和细胞因子可诱导Blimp-1。尽管存在一些共性,但Blimp-1在B细胞和T细胞中的不同靶标和调节因子表明这种调节机制存在有趣的进化差异。