Manipulation of B-cell responses with histone deacetylase inhibitors

Michaela Waibel, Ailsa Jane Christiansen, Margaret Hibbs, Jake Shortt, Sarah Jones, Ian Simpson, Amanda Light, Kristy O'Donnell, Eric Francis Morand, David M Tarlinton, Ricky W Johnstone, Edwin Hawkins

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Histone deacetylase inhibitors (HDACi) are approved for treating certain haematological malignancies, however, recent evidence also illustrates they are modulators of the immune system. In experimental models, HDACi are particularly potent against malignancies originating from the B-lymphocyte lineage. Here we examine the ability of this class of compounds to modify both protective and autoimmune antibody responses. In vitro, HDACi affect B-cell proliferation, survival and differentiation in an HDAC-class-dependent manner. Strikingly, treatment of lupus-prone Mrl/lpr mice with the HDACi panobinostat significantly reduces autoreactive plasma-cell numbers, autoantibodies and nephritis, while other immune parameters remain largely unaffected. Immunized control mice treated with panobinostat or the clinically approved HDACi vorinostat have significantly impaired primary antibody responses, but these treatments surprisingly spare circulating memory B cells. These studies indicate that panobinostat is a potential therapy for B-cell-driven autoimmune conditions and HDACi do not induce major long-term detrimental effects on B-cell memory.
Original languageEnglish
Pages (from-to)1 - 12
Number of pages12
JournalNature Communications
Issue number(Art. No: 6838)
Publication statusPublished - 2015

Cite this

Waibel, M., Christiansen, A. J., Hibbs, M., Shortt, J., Jones, S., Simpson, I., Light, A., O'Donnell, K., Morand, E. F., Tarlinton, D. M., Johnstone, R. W., & Hawkins, E. (2015). Manipulation of B-cell responses with histone deacetylase inhibitors. Nature Communications, 6((Art. No: 6838)), 1 - 12.