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Function of Protein Kinase CK2 in B-Cells in the Pathogenesis of Autoimmune Disease

Undergraduate #49
Discipline: Biological Sciences
Subcategory: Cancer Research
Session: 4
Room: Exhibit Hall A

Rhythm Williams - Lawson State Community College
Co-Author(s): Hairong Wei, Wei Yang, Etty N. Benveniste and Hongwei Qin; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL



B-cells are key regulators in the pathogenesis of autoimmune diseases as antibody secreting cells, antigen-presenting cells and cytokine producing cells. The function of B cells in the pathogenesis of Multiple Sclerosis (MS) have received increasing attention as the success of clinical trials of B-cell depleting therapies and the presence of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF). Protein Kinase CK2 is overexpressed and overactive in B-cell leukemia and B-cell lymphomas, leading to inappropriate activation of NF-kB, JAK/STAT and PI3K/AKT/mTOR signaling. However, little is known about the function of CK2 in B-cell development and differentiation, and specifically, in the pathogenesis of MS and its animal model, Experimental Autoimmune Encephalomyelitis (EAE). I hypothesize that CK2 kinase activity in B-cells affects B-cell inflammatory responses during EAE disease progression. Our results indicate CK2 mRNA and protein expression is induced upon B-cell activation. We generated CK2afl/flCD19CreTg/+ (CD19-CK2aKO) mice, which have CK2a deletion at the earliest stages and throughout B-cell development. We confirmed the deletion efficiency using B-cells isolated from WT and CD19-CK2aKO mice. Furthermore, our studies demonstrate that CK2a specific deletion in B-cells results in exacerbated EAE disease severity. Our studies elucidate the critical function of CK2a in B-cell activation, which are important in regulating immune responses in autoimmune diseases such as MS and EAE.

Funder Acknowledgement(s): Hairong Wei, Wei Yang, Etty N. Benveniste and Hongwei Qin; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL

Faculty Advisor: Dr. Shawanda Thomas, sthomas@lawsonstate.edu

Role: I conducted the experiments for Western Blotting, the results for genotyping, and quantitative real time polymerase chain reaction (PCR). I confirmed the specific gene target knockout at all 3 levels. I also extracted RNA to get the data for the quantitative real time PCR.

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This material is based upon work supported by the National Science Foundation (NSF) under Grant No. DUE-1930047. Any opinions, findings, interpretations, conclusions or recommendations expressed in this material are those of its authors and do not represent the views of the AAAS Board of Directors, the Council of AAAS, AAAS’ membership or the National Science Foundation.

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