Regulation of Immunoglobulin Gene Rearrangement by a Chimeric Mouse-Human Transgene.
MetadataShow full item record
Immunoglobulin (Ig) genes undergo DNA rearrangement (termed VDJ rearrangement) during B cell development to produce antibodies. The regulation of VDJ rearrangement during B cell development is highly regulated. Once the heavy chain VDJ gene segments are successfully rearranged, a heavy chain protein is made. Normally, this heavy chain signals the cell to stop heavy chain VDJ rearrangement and to initiate light chain VJ rearrangement. Our transgenic mice express the HUG (1 heavy chain transgene at high levels. This transgenic heavy chain inhibits endogenous heavy chain rearrangement, but unexpectedly does not induce light chain rearrangement. This is the first demonstration that the mechanism regulating heavy chain rearrangement can be distinguished from that regulating light chain rearrangement. My project is to develop an in vitro assay for studying this differential signaling. This involves hybridomas that are HUG+?-, therefore resulting in no light chain rearrangement. I will then transfect a rearranged endogenous heavy chain (?) and look at the production and association of the light chain protein.