During fiscal year 2011, we accomplished the following: 1. Initiated studies to examine the rapid down-regulation of hundreds of mRNAs in nave splenic B lymphocytes activated by a single pulse of B cell receptor (BCR) signaling. The working hypothesis is that these mRNA are rapidly degraded due to functional alterations in RNA binding proteins or micro RNA (miRs) in response to pulsed BCR signaling. We began by comparing the 3 untranslated regions of these mRNA and signal-induced changes in RNA binding proteins. 2. We assayed changes in miR expression as a function of time in splenic B cells activated via the BCR. 3. To determine the function of Rel proteins in B cell priming, we generated p50/Rel double-knock out mice. We previously showed that priming efficiency was reduced in Rel-deficient B cells. We will now compare priming efficiency in p50 null, Rel null and p50/Rel double null B cells. Conversely, we will evaluate whether p50/Rel T cells are capable of providing B cell help via induction of CD40L and other co-stimulatory molecules.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000376-04
Application #
8335846
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2011
Total Cost
$287,514
Indirect Cost
Name
National Institute on 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
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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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