The Crucial Role of A20 in Human B Cell Function: Implications for Immunoregulation and Autoimmunity

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B612
Abstract ID: 5897

Presenting Author:
Rachel E Sutton , Graduate Student at Emory Univ. Sch. of Med.

Abstract:

Autoimmune diseases, such as systemic lupus erythematosus (SLE), are underscored by dysregulated B cell function including the production of autoantibodies, skewed population ratios, and aberrant signaling. Given that the family of nuclear factor kappa B (NF-kB) transcription factors govern responses to stimuli, survival, differentiation, and so forth understanding the intricate regulatory network of NF-kB in B cell biology is paramount for unraveling treatments for B cell-linked autoimmune diseases. Here, we focus on a negative regulator of NF-kB signaling, A20 (TNFAIP3), that deactivates NF-kB transcription factor translocation through the ubiquitination and deubiquitination of target proteins. Haploinsufficiency in A20 results in an autoimmune phenotype and mutations to A20 have been associated with SLE, suggesting implications to B cell function. To investigate the role of A20 in B cell signaling, we generated a TNFAIP3 knockout (KO) human B cell line. We then stimulated KO and WT cells with agonists such as B-cell activating factor (BAFF), CD40L, anti-IgM, TNFa, and R848 that activated distinct modes of NF-kB signaling. Using a combination of qRT-PCR, western blotting, and flow cytometry, the differences in gene expression patterns, protein production, and activation of NF-kB transcription factors were evaluated. Together, these findings provide a framework to understand how A20 controls B cell signaling and contributes to B cell-regulated autoimmune diseases.