The cis-acting regulatory elements of immunoglobulin heavy chain gene involved in enhanced immunoglobulin production after lipopolysaccharide (LPS) stimulation.

In the present study, the transient expression of the human immunoglobulin heavy chain gene (HIG1) was analyzed in a mouse pre-B-cell line, 70Z/3, after LPS stimulation. HIG1 gene and its recombinant plasmids were transfected by the calcium phosphate method into 70Z/3 cells and the cells were stimulated with lipopolysaccharide (LPS) 48 hr after DNA transfection. The amounts of human heavy chain gene products greatly increased in 70Z/3 cells after LPS stimulation, but the increment was diminished by deletion of the heavy chain gene enhancer element (MluI-HpaI fragment) in the J-C intron from the HIG1 gene. The gene, delta 3, which contained the 5' promoter region and the rearranged VDJ region of HIG1 but lacked the enhancer element, was weakly transcribed in 70Z/3 cells after LPS stimulation. Insertion of the enhancer element into the delta 3 gene greatly enhanced the transcription of the VDJ gene. The highest enhancement of the VH gene transcription rate was obtained when the 3' half of the enhancer element was ligated to the delta 3 gene. The present data suggest that the 3' half of the enhancer element of the heavy chain gene may play an important role in the enhanced production of immunoglobulin which is induced with LPS stimulation.