Identification and regulation of genes important for B lymphocyte activation


Project leader


Funding source

Swedish Research Council - Vetenskapsrådet (VR)


Project Details

Start date: 01/01/2007
End date: 31/12/2009
Funding: 1500000 SEK


Description

B lymphocytes change adhesive and migratory properties and switch Immunoglobulin (Ig) class during activation by antigen in vivo. Similar responses occur when B cells are activated in vitro. I wish to identify proteins, which regulate the B cell morphology, by microarray analysis. Selected genes will be introduced via retroviral transduction into B cells and tested for function. The genes will also be knocked down using RNA interference. At later stages, transgenic and knockout mice will be made. Ig class switching occurs after a DNA recombination event, and is regulated by so-called germline transcripts. I intend to study the importance of the Ig heavy (H) chain 3´ enhancers for germline transcription and class switch recombination (CSR). We have made three transgenic lines, expressing the epsilon region and the 3´ enhancers and found that one of them can recruit the recombination/somatic mutation machinery. The latter has previously been shown to be dependent on Activation induced cytidine deaminase (AID). We wish to further study these transgenic lines to be able to identify the factors that are involved in CSR, in part by backcrossing to different knockout strains. In addition, we wish to make new transgenic lines, including new regions of the IgH locus. These studies are important to increase the knowledge of B cells function and how production of Ig isotypes is regulated. They can become important for the treatment of immune-related diseases.

Last updated on 2017-31-03 at 12:58