Abstract
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 start light chain VJ rearrangement. Our transgenic mice express the HUG g1 heavy chain transgene at high levels.This transgenic heavy chain inhibits endogenous heavy chain rearrangement, but unexpectedly does not induce light rearrangement. This is the first demonstration that the mechanism that regulating heavy chain rearrangement can be distinguished from that regulating light chain rearrangement.My project is to develop an <i style="mso-bidi-font-style:normal">in vitro assay for studying this differential signaling.This involves hybridomas that are HUG+m-, and therefore results in no light chain rearrangement. I have transfected a rearranged endogenous heavy chain into two different cell lines and antibiotic selection is underway. I will then assay for production and association of the light chain protein.
