NF-kB activation and function in B lymphocytes

National Institute On Aging

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Abstract

During FY15 we accomplished the following: 1) We completed studies of tonic and acute BCR survival signaling that maintains B cell homeostasis. We found evidence for two forms of post-transcriptional survival signaling. A manuscript describing these studies has been submitted for publication. 2) We extended studies of signal-independent B cell proliferation. We obtained evidence for reduced phosphatase activity in the G2/M phase that resulted in a late G1 phenotype of post-mitotic cells. Additionally, expression of survivin exclusively in the G1 phase of post-mitotic cells indicated that it may be involved in signal-independent proliferation. Accordingly, we found that the surviving inhibitor LLP3 blocked G1 progression in post-mitotic cells. 3) We purified follicular and marginal zone B cells from spleens of mice that lack each subunit of NF-κB proteins. Gene expression analyses from these cells will be the first to identify differences in B cells that lack these components. 4) We carried out additional ChIP-Seq studies to identify p65/RelA, Rel and RelB binding sites genome-wide in primary B cells activated via the B cell receptor and CD40. These studies of inducible DNA binding by NF-κB family members will be used to identify relationships between transcription activation and NF-κB recruitment in activated B cells. 5) We developed ATAC-Seq protocol to more accurately identify DNase I hypersensitive sites genome-wide in activated primary B cells.