Abstract
B cells play a central role in immune system function. Deregulation of normal B cell maturation can lead to the development of autoimmune syndromes as well as B cell malignancies. Elucidation of the molecular features of normal B cell development is important for the development of new target therapies for autoimmune diseases and B cell malignancies. Employing B cell-specific conditional knockout mice, we have demonstrated here that the transcription factor leukemia/lymphoma-related factor (LRF) forms an obligate dimer in B cells and regulates mature B cell lineage fate and humoral immune responses via distinctive mechanisms. Moreover, LRF inactivation in transformed B cells attenuated their growth rate. These studies identify what we believe to be a new key factor for mature B cell development and provide a rationale for targeting LRF dimers for the treatment of autoimmune diseases and B cell malignancies.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / immunology*
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B-Lymphocytes / physiology
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Cell Differentiation / immunology
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Cyclin-Dependent Kinase Inhibitor p16 / genetics
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Cyclin-Dependent Kinase Inhibitor p16 / immunology
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / immunology*
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Gene Expression Regulation
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Germinal Center / cytology
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Germinal Center / immunology*
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Germinal Center / physiology
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Mice
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Mice, Knockout
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Microarray Analysis
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Models, Molecular
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Protein Conformation
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Protein Multimerization
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Spleen / cytology
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Transcription Factors / chemistry
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Transcription Factors / genetics
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Transcription Factors / immunology*
Substances
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Cdkn2a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p16
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DNA-Binding Proteins
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RNA, Small Interfering
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Transcription Factors
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Zbtb7a protein, mouse