Pre-B cell-specific lambda 5 gene expression due to suppression in non pre-B cells

Abstract

The lambda 5 gene is expressed specifically in pre-B cells; during B lymphocyte differentiation the expression of the lambda 5 gene is turned on in pre-B cells and turned off again at the mature B cell stage. No other cell type has yet been found to express the lambda 5 gene. The pre-B cell-specific expression of the lambda 5 gene is regulated at the level of transcription. We asked whether the region 5' of the lambda 5 gene (5' lambda 5) could explain the stage- and tissue-specific expression. The lambda 5 promoter lacks a TATA box and transcription is initiated at multiple sites. In the presence of a heterologous enhancer, 5' lambda 5 confers pre-B cell-specific expression on the reporter gene chloramphenicol acetyl-transferase. Deletion analysis of 5' lambda 5 defines two separate regions, referred to as A lambda 5 and B lambda 5. Region B lambda 5 suppresses the expression in non pre-B cells since deletion of B lambda 5 allows A lambda 5 to promote transcription of the reporter gene in in all cell types tested. In addition, B lambda 5 acts as an enhancer on the heterologous kappa light chain promoter in pre-B cells but not in B cells. Thus region A lambda 5 functions as a basal promoter in all cell types tested. Region B lambda 5, in concert with a heterologous enhancer, acts as a suppressing region in non-pre-B cells and therefore confers pre-B cell specificity on the expression of the lambda 5 gene.