Division of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
Immunol Rev. 2012 May;247(1):107-19. doi: 10.1111/j.1600-065X.2012.01116.x.
The germinal center (GC) is a unique histological structure found in peripheral lymphoid organs. GCs provide an important source of humoral immunity by generating high affinity antibodies against a pathogen. The GC response is tightly regulated during clonal expansion, immunoglobulin modification, and affinity maturation, whereas its deregulation has a detrimental effect on immune function, leading to development of diseases, such as lymphoma and autoimmunity. LRF (lymphoma/leukemia-related factor), encoded by the ZBTB7A gene, is a transcriptional repressor belonging to the POK (POZ and Krüppel)/ZBTB (zing finger and BTB) protein family. LRF was originally identified as a PLZF (promyelocytic leukemia zinc finger) homolog that physically interacts with BCL6 (B-cell lymphoma 6), whose expression is required for GC formation and associated with non-Hodgkin's lymphoma. Recently, our group demonstrated that LRF plays critical roles in regulating lymphoid lineage commitment, mature B-cell development, and the GC response via distinct mechanisms. Herein, we review POK/ZBTB protein function in lymphoid development, with particular emphasis on the role of LRF in GC B cells.
生发中心（GC）是在外周淋巴器官中发现的一种独特的组织学结构。GC 通过产生针对病原体的高亲和力抗体，为体液免疫提供了重要的来源。GC 反应在克隆扩增、免疫球蛋白修饰和亲和力成熟过程中受到严格调控，而其失调对免疫功能有不利影响，导致疾病的发生，如淋巴瘤和自身免疫性疾病。LRF（淋巴瘤/白血病相关因子），由 ZBTB7A 基因编码，是一种转录抑制因子，属于 POK（POZ 和 Krüppel）/ZBTB（锌指和 BTB）蛋白家族。LRF 最初被鉴定为 PLZF（早幼粒细胞白血病锌指）同源物，它与 BCL6（B 细胞淋巴瘤 6）物理相互作用，BCL6 的表达是 GC 形成所必需的，与非霍奇金淋巴瘤有关。最近，我们的研究小组表明，LRF 通过不同的机制在淋巴样细胞谱系的决定、成熟 B 细胞的发育和 GC 反应中发挥关键作用。本文综述了 POK/ZBTB 蛋白在淋巴样发育中的功能，特别强调了 LRF 在 GC B 细胞中的作用。
