Manipulation of B-cell responses with histone deacetylase inhibitors

作者：Waibel Michaela; Christiansen Ailsa J; Hibbs Margaret L; Shortt Jake; Jones Sarah A; Simpson Ian; Light Amanda; O'Donnell Kristy; Morand Eric F; Tarlinton David M; Johnstone Ricky W; Hawkins Edwin D^*

来源：Nature Communications, 2015, 6(1): 6838.

DOI：10.1038/ncomms7838

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.

• 出版日期2015-4
• 单位河北医科大学