Characterizing the role of IRF5 in human B cell development and function — ASN Events
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  2. Poster Session 1
  3. Characterizing the role of IRF5 in human B cell development and function

Characterizing the role of IRF5 in human B cell development and function (#241)

Saurav De 1 2 , Di Feng 1 , Peicheng Du 3 , Robert Donnelly 4 5 , Betsy Barnes 1
  1. Rutgers Biomedical and Health Sciences University, Newark, NJ, United States
  2. Rutgers Graduate School of Biomedical Sciences, Newark, , New Jersey, USA
  3. High Performance and Research Computing Group, Office of Information Technology, Rutgers University, Newark, New Jersey, USA
  4. Department of Pathology and Laboratory Medicine and NJMS Molecular Resource Facility, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA
  5. Department of Pathology and Laboratory Medicine and NJMS Molecular Resource Facility, Rutgers Biomedical and Health Sciences, Newark, New Jersey, USA

The transition of naïve B cells to effector B cells is dependent on a large transcription factor network, which mediates both effector B cell differentiation and function.  The full repertoire of transcription factors involved in this process is not known, yet dysregulation of this transcription factor network can result in altered B cell function and autoimmunity.  Work from our lab, as well as others, has suggested that the transcription factor, interferon regulatory factor 5 (IRF5), is involved in the development of effector B cells.  Irf5-/-mice have previously been reported to have reduced plasma B cells, as well as reduced serum IgG subtypes.  It remains unclear, however, what role IRF5 may play in human B cell development and function.  We find significant levels of IRF5 in B cells translocate to the nucleus following stimulation with anti-IgM antibody and CpG.   In order to characterize the role of IRF5 in human B cells, we have performed IRF5 ChIP-Seq in both primary naïve B cells and Ramos B cells either mock or anti-IgM and CpG treated.   Genes associated with plasma B cell development were significantly enriched following activation, suggesting IRF5 plays a critical role in the differentiation of plasma B cells.  To further characterize the role of IRF5 in primary human B cells, we have been able to successfully perform siRNA-mediated knockdown of IRF5. Knockdown of IRF5 did not show significant impact on cell viability, however, reduced inflammatory cytokine expression was seen.  These data highlight the multi-functional role of IRF5 in regulating both human B cell differentiation and function.