POK/ZBTB proteins: an emerging family of proteins that regulate lymphoid development and function

Authors

  • Sung-Uk Lee,

    1. Division of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
    2. Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
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  • Takahiro Maeda

    1. Division of Hematopoietic Stem Cell and Leukemia Research, Beckman Research Institute of City of Hope, Duarte, CA, USA.
    2. Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
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Takahiro Maeda
Division of Hematology, Department of Medicine
Brigham and Women’s Hospital
Harvard Medical School
1 Blackfan Circle
Boston, MA, 02115 USA
Tel.: +1 617 355 9115
Fax: +1 617 355 9124
e-mail: tmaeda@partners.org

Abstract

Summary:  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.

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