MYOCYTE ENHANCER FACTOR-RELATED B-MEF2 IS DEVELOPMENTALLY EXPRESSED IN B-CELLS AND REGULATES THE IMMUNOGLOBULIN J-CHAIN PROMOTER

Immunoglobulin J chain gene expression is induced by the delivery of a lymphokine signal to antigen-activated B cells in a primary immune re sponse. A major interleukin 2 (IL-2)-responsive region that contains t wo adjacent control elements (JA and JB) exists within the J chain pro moter. Transcription factor PU.1 positively regulates J chain gene exp ression by binding to one of the control elements (JB) in the J chain promoter. In the present study we have determined that a myocyte enhan cer factor 2 (MEF2)-related nuclear factor, named B-MEF2, positively r egulates the J chain gene promoter activity via the second control ele ment (JA), An in vitro translated MEF2 family member, MEF2C, was found to bind the JA site with identical properties as endogenously express ed B-MEF2 in B cell lines. Moreover, in vivo experiments showed that a dominant negative mutant of MEF2C blocked B-MEF2 regulation of the J chain promoter. Consistent with its role as positive regulator of J ch ain gene expression, B-MEF2 levels were enhanced in highly differentia ted B cells. In addition, induction of an IL-2-responsive presecretor cell line BCL1 with IL-2 or IL-5 (which up-regulates J chain gene expr ession) resulted in an increased expression of B-MEF2. We conclude tha t a MEF2-related transcriptional factor, B-MEF2, acts as a stage-speci fic positive regulator of J chain gene expression in the B cell lineag e.