August 3, 2017

HDAC3 role in B-cell development

The histone deacetylase HDAC3 is required for the maturation of B cells, white blood cells that produce antibodies.

Histone deacetylases (HDACs) are enzymes that modulate gene expression and have important roles in development and disease. HDAC inhibitors are active against lymphoma, and understanding the roles of specific HDACs is important for further therapeutic development.

Scott Hiebert, Ph.D., and colleagues used a mouse model to explore the role of HDAC3 in the early development of B cells, white blood cells that produce antibodies.

They found that inactivation of HDAC3 impaired B-cell development before the formation of a functional B-cell receptor (a membrane bound antibody). The researchers demonstrated an unexpected role for HDAC3 in “VDJ recombination” – the process that generates antibodies and immune diversity.

Using bone marrow transplantation, they further showed that the deacetylase activity of HDAC3 is required for B-cell receptor production and B-cell maturation.

The findings, reported in the Proceedings of the National Academy of Sciences, confirm the importance of HDAC3 deacetylase activity and suggest that HDAC3-specific inhibitors may be therapeutically useful for B-cell cancers.

This research was supported by the T. J. Martell Foundation; the Robert J. Kleberg, Jr., and Helen C. Kleberg Foundation; National Institutes of Health Grants CA109355, CA164605, and CA064140; core services performed through Vanderbilt Digestive Disease Research Center (NIH grant DK058404); the Vanderbilt-Ingram Cancer Center (NIH grant CA068485); and by NIH Grant RR028106 for the Next Generation Nucleic Acid Sequencer, housed in VANTAGE.

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