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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000376-08
Application #
9147292
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Lee-Chang, Catalina; Bodogai, Monica; Moritoh, Kanako et al. (2016) Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers. J Immunol 196:3385-97
Kaileh, Mary; Vazquez, Estefania; MacFarlane 4th, Alexander W et al. (2016) mTOR-Dependent and Independent Survival Signaling by PI3K in B Lymphocytes. PLoS One 11:e0146955
Fowler, Trent; Garruss, Alexander S; Ghosh, Amalendu et al. (2015) Divergence of transcriptional landscape occurs early in B cell activation. Epigenetics Chromatin 8:20
Maul, Robert W; Cao, Zheng; Venkataraman, Lakshmi et al. (2014) Spt5 accumulation at variable genes distinguishes somatic hypermutation in germinal center B cells from ex vivo-activated cells. J Exp Med 211:2297-306
Kaileh, Mary; Sen, Ranjan (2012) NF-ýýB function in B lymphocytes. Immunol Rev 246:254-71
Sen, Ranjan (2011) The origins of NF-?B. Nat Immunol 12:686-8
Olkhanud, Purevdorj B; Damdinsuren, Bazarragchaa; Bodogai, Monica et al. (2011) Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4? T cells to T-regulatory cells. Cancer Res 71:3505-15
Fowler, Trent; Sen, Ranjan; Roy, Ananda L (2011) Regulation of primary response genes. Mol Cell 44:348-60
Damdinsuren, Bazarragchaa; Zhang, Yongqing; Khalil, Ashraf et al. (2010) Single round of antigen receptor signaling programs naive B cells to receive T cell help. Immunity 32:355-66
Sen, Ranjan; Smale, Stephen T (2010) Selectivity of the NF-{kappa}B response. Cold Spring Harb Perspect Biol 2:a000257

Showing the most recent 10 out of 12 publications