NF-kB activation and function in B lymphocytes

National Institute On Aging

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Abstract

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.