Deletion of the Igκ Light Chain Intronic Enhancer/Matrix Attachment Region Impairs but Does Not Abolish VκJκ Rearrangement

AbstractRoles of the κ intronic enhancer (iEκ) and its asssociated matrix attachment region (MAR) during B cell development were examined using mutant embryonic stem (ES) cell lines in which the entire region on both chromosomes was replaced with either a recombined LoxP site (EκND) or the PGK–neomycin resistance (PGK-neor) gene (EκNI). B cells derived from EκND ES cells had greatly impaired VκJκ rearrangement, normal levels of κ expression, and κ:λ ratios of 1:1 instead of the usual 10:1. Furthermore, λ-producing hybridomas derived from EκND cells displayed little κ rearrangement. Thus, the MAR and iEκ are quantitatively significant for κ rearrangement but not necessary. In addition, little VκJκ rearrangement could be detected in B cells derived from EκNI ES cells, demonstrating that an inserted PGK–neor gene dominantly suppresses VκJκ rearrangement