REGULATION OF PROMOTER AND INTRON ENHANCER ACTIVITY IN IMMUNOGLOBULINHEAVY-CHAIN GENES DURING B-CELL DIFFERENTIATION

Chloramphenicol acetyltransferase (CAT) transgenic mice, in which the transgene is regulated by the VH promoter and heavy-chain intron enhan cer (ECL), were examined to investigate the variation of activity of t hese cis-acting elements during the late stage of B-cell development, CAT enzyme activity decreased when resting B cells were stimulated thr ough B-cell receptors (BCR) with goat anti-mouse IgM antibodies in vit ro. On the other hand, when these B cells were stimulated by lipopolys accharide (LPS) in vitro, they showed enhanced CAT activity, accompani ed by an increase in the number of CD43(+) B220(+) cells (pro-plasma a nd plasma cells). In addition, the CAT activities in CD43(+) B220(+) a nd PNA(hi) B220(+) cells from immunized mice were higher than those in CD43(-) B220(+) and PNA(lo) B220(+) cells, respectively. These result s suggest that the activity of E mu in the context of VH promoter was transiently down-regulated by stimulation through the BCR but enhanced at the pro-plasma and plasma stages.