Journal
IMMUNOLOGICAL REVIEWS
Volume 247, Issue -, Pages 107-119Publisher
WILEY
DOI: 10.1111/j.1600-065X.2012.01116.x
Keywords
germinal center; leukemia; lymphoma related factor; POKEMON; ZBTB; POZ; POK
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Funding
- STOP Cancer
- V Foundation
- Margaret E. Early Medical Research Trust
- Tim Nesvig Lymphoma Research Fund
- American Society of Hematology
- NIH [1R01AI084905-01A1]
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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 Kruppel)/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-Hodgkins 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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