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Abstracts (complete list) - Wissenschaft Online

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Andreas Brandl, Juergen Wittmann, Michael Boesl, Hans-Martin Jaeck<br />

MicroRNA-Mediated Control of B Cell Activation<br />

MicroRNAs (miRNAs) constitute a growing class of small noncoding RNAs that regulate<br />

gene expression mainly at the posttranscriptional level. The regulatory function of<br />

miRNAs has recently been shown to play critical roles in the control of hematopoiesis.<br />

The goal of this project is to determine whether miRNAs function also during the<br />

antigen-induced activation of B lymphocytes. To determine the miRNA profiles in naive<br />

B cells before and after polyclonal activation, we stimulated B cells isolated via magnetic<br />

CD43 beads from spleen with either LPS (simulates T cell-independent activation) or<br />

with a combination of anti-IgM, anti-CD40 and IL4 (simulates T cell-dependent<br />

activation) for various times. The analysis of isolated RNA using miRNA microarray- and<br />

qRT-PCR assays identified about 104 miRNAs in unstimulated B cells. 35 of these were<br />

mostly downregulated after stimulation. In silico analyses with various miRNA target<br />

prediction programs revealed a very interesting and promising set of potential<br />

transcripts whose translation/stability could be controlled by miRNAs during the antigeninduced<br />

activation phase of mature B cells. Among these targets are BCR signalling<br />

molecules and transcription factors that control proliferation, IgH class switch as well as<br />

differentiation in antibody-secreting plasma cells. We will now verify biochemically<br />

potential targets for each the differentially regulated miRNAs and determine the effect<br />

of retrovirally transduced miRNAs on B cell development.

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