Selective HDAC6 Inhibition Corrects Aberrant B Cell Development in the Bone Marrow of NZB/W F1 Mice

B cell development in the bone marrow is highly complex and includes vital regulatory checkpoints to maintain central tolerance. Defects in central tolerance are implicated in systemic lupus erythematosus (SLE) and aberrant B cell development has been reported in NZB/W mice.

We hypothesized that altered B cell development in the bone marrow of lupus-prone NZB/W mice would be corrected after HDAC6 inhibition. B cell development was evaluated by flow cytometric analysis of Hardy fractions from bone marrow cells of NZB/W mice treated with an HDAC6 inhibitor or vehicle control.

Additionally, deep sequence analysis of RNA from the bone marrow was utilized to identify potential targets of HDAC6. As NZB/W mice aged, there was an apparent shift in later stages of B cell development suggesting accelerated progression through maturation and potential to bypass key regulatory checkpoints.

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