Investigations in this group currently focus on the regulation of the J chain gene in B lymphocytes and the function of the J chain protein. The human J chain gene was cloned in our lab several years ago to compare its regulation to that of immunoglobulin genes. Our analysis of the promoter has in the past year clarified three regions essential for promoter function; deletion of any one of these region reduces by about 90% the expression of a reporter gene transfected into the murine myeloma S194. One region, about 400 bp upstream of the transcriptional initiation site, contains three repeats of the hexamer CCTTCA. The second, about 300 bp upstream of the initiation site , contains a """"""""kappa-B"""""""" element similar to those found in regulatory sequences of ti immunoglobulin kappa gene, the Human Immunodeficiency Virus, and several other genes of the immune system. The third region contains a hexamer identical to protein. We are also attempting to explore the function of the J chain by determining the immunologic consequences of the los of J chain gene function. Because no natural J chain deficiencies have been described, we are attempting to create a mouse strain in which the normal J chain gene has been in activated. To this end we have constructed a modified mouse J chain gene which has been transfected into mouse embryonic stem cells. Cells in which our inactive J chain gene construct has replaced a copy of the normal gene by homologous recombination will be used to derive live mice with no active J chain gene. The immunologic consequences of this loss will be examined.
