Deletion of a B-cell-specific enhancer affects transfected, but not endogenous, immunoglobulin heavy-chain gene expression

Abstract

A transcriptional enhancer has recently been identified between the variable and constant region coding segments of an assembled immunoglobulin heavy-chain gene. This enhancer is required for efficient expression of such genes when transfected into myeloma cells. A class switch rearrangement in the mouse myeloma cell line 9.9.2.1 has resulted in deletion of this enhancer, and yet this cell line continues to produce heavy chains at a high level. Cell line 9.9.2.1 is a gamma 2a-producing class-switch variant derived from the gamma 2b-producing myeloma cell line, MPC11. We demonstrate that despite the high level of heavy-chain production in 9.9.2.1, the cloned 9.9.2.1 heavy-chain gene is not expressed efficiently when transfected into myeloma cells. Efficient expression after transfection can be obtained only if the deleted enhancer is reinserted into the gene. The implication of this finding for the role of this enhancer in establishing and/or maintaining immunoglobulin heavy-chain gene expression is discussed.