HDAC7 is essential in early pre-germinal center formation and its deregulation is associated with DLBCL [Xenografts]

Histone deacetylase HDAC7 is required for early B cell development and governs the acquisition of B cell progenitors gene identity. In addition, HDAC7 has been identified as a novel biomarker and prognosis factor in infant pro-B-ALL. However, its role in mature B cell biology and associated malignancies is unknown. Here, by using a conditional mouse model for specific deletion in activated B cells, we demonstrate that HDAC7 is essential for the entry and initiation of the germinal center (GC) reaction. HDAC7 deficiency results in the blockade of B cell development at the pre-GC stage, leading to the generation of aberrant GC B cells, diminished class switch recombination and plasma cell formation. We demonstrate that, while it is generally underexpressed in diffuse large B cell lymphoma (DLBCL) tumors, the low expression of HDAC7 is associated with a poor prognosis of the patients. Importantly, exogenous expression of HDAC7 in DLBCL cell lines reduces the proliferative capacity of these latter, as well as DLBCL tumorigenecity in vivo. In summary, our data revealed first, the essential function of HDAC7 in the establishment of the GC, and second, the potential contribution of HDAC7 deregulation in DLBCL development. Overall design: Cells were extracted from subcutaneosly injected MD901 cell line transfected with a two-step retroviral infection that allowed the ectopic expression of HDAC7 upon doxycicline induction. Doxicycline was added to the drinking water. Tumor was extrated and disgregated to obtain a single cell suspension. RNA was extracted using the Quiagen kit for RNA extraction. Samples were quantified and subjected to quality control using a Bioanalyzer apparatus (IRB, Barcelona). Samples were processed by Macrogene, Inc.