During FY13, we accomplished the following: 1) Continued analysis of P3 and P4 populations to understand the basis for stimulus-independent cell-cycle progression of P4 cells. RNA from purified P3/P4 cells were examined by microarrays and whole cell extracts were probed for cell-cycle associated proteins. Immunoprecipitation studies to identify APC-associated proteins are underway. We also utilized new DNA synthesis marker EdU to precisely define the cell cycle status of P3 and P4 populations. These studies have led to a fuller characterization of these cell populations. Additionally, we investigated whether all forms of B cell stimulation resulted in cells with similar characteristics. We found that P3/P4 equivalent cells present after LPS stimulation behaved similarly to P3/P4 cells generated after treatment with anti-CD40. That is, only P4 cells continued to divide in the absence of additional stimulation. However, both P3 and P4 populations obtained after anti-Ig treatment proliferated without additional stimulation. 2) Generated stable transfectants in BJAB cells to test the hypothesis that NF-κB-dependent promoters communicate with 3UTRs to regulate mRNA lifetime of target genes. 3) Identified long intergenic non-coding RNAs that were induced in response to BCR signaling. 4) Collaborated with Ananda Roy (Tufts University Medical School) and Ali Shilatifard (Stowers Institute) to map the genome-wide H3K4me3 and H3K27me3 status in naive B cells, and cells activated via the BCR and by LPS after short-term treatment (30 min and 2h). This time-course was designed to study immediate-early gene expression in response to defined stimuli.
| 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 |
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