Abstract：
Antibody secreting plasma cell plays an indispensable role in humoral immunity. As activated B cell undergoes germinal center reaction and develops into plasma cell, it gradually loses B cell characteristics and embraces functional changes associated with immunoglobulins production. Differentiation of B cell into plasma cell involves drastic changes in cell structure, granularity, metabolism, gene expression and epigenetic regulation that couple with the mounting capacity for synthesis of a large quantity of antigen-specific antibodies. The interplay between three hallmark transcriptional regulators IRF4, BLIMP1, and XBP1, is critical for supporting the cellular reprograming activities during B to plasma cell transition. IRF4 promotes plasma cell generation by directing immunoglobulin class switching, proliferation and survival; BLIMP1 serves as a transcriptional repressor that extinguishes B cell features; whereas XBP1 controls unfolded protein response that relieves endoplasmic reticulum stress and permits antibody release during terminal differentiation. Intriguingly, high expression of IRF4, BLIMP1, and XBP1 molecules have been reported in myeloma cells derived from multiple myeloma patients, which negatively impact treatment outcome, prognosis, and relapse frequency. Despite the introduction of immunomodulatory drugs in recent years, multiple myeloma is still an incurable disease with poor survival rate. An in-depth review of IRF4, BLIMP1, and XBP1 triad molecules in plasma cell generation and multiple myeloma tumorigenesis may provide clues to the possibility of targeting these molecules in disease management.
摘要：
分泌抗体的浆细胞在体液免疫中起着不可或缺的作用。当活化的B细胞经历生发中心反应并发展成浆细胞时，它逐渐失去B细胞特征，并包含与免疫球蛋白产生相关的功能变化。B细胞分化为浆细胞涉及细胞结构的急剧变化，粒度,新陈代谢，基因表达和表观遗传调控，与大量抗原特异性抗体的合成能力相结合。三个标志性转录调节因子IRF4，BLIMP1和XBP1之间的相互作用对于支持B到浆细胞过渡期间的细胞重编程活性至关重要。IRF4通过指导免疫球蛋白类别转换促进浆细胞生成，增殖和存活；BLIMP1作为转录抑制因子，可以消除B细胞特征；而XBP1控制未折叠的蛋白质反应，从而缓解内质网应激并允许抗体在终末分化过程中释放。有趣的是，IRF4，BLIMP1和XBP1分子在多发性骨髓瘤患者的骨髓瘤细胞中高表达，对治疗结果产生负面影响，预后,和复发频率。尽管近年来出现了免疫调节药物，多发性骨髓瘤仍然是一种无法治愈的疾病，存活率低。对IRF4，BLIMP1和XBP1三联体分子在浆细胞生成和多发性骨髓瘤肿瘤发生中的深入研究可能为在疾病管理中靶向这些分子的可能性提供线索。
