Molecular Basis of Heavy-Chain Class Switching and Switch Region Deletion in an Abelson Virus-Transformed Cell Line

Abstract

We demonstrated that a subclone of an Abelson murine leukemia virus-transformed B-lymphoid cell line switched from μ to γ_2b expression in vitro, by the classical recombination-deletion mechanism. In this line, the expressed V_HDJ_H region and the C_γ2b constant region gene were juxtaposed by a recombination event which linked the highly repetitive portions of the S_μ and S_γ2b regions and resulted in the loss of the C_μ gene from the intervening region. An additional recombination event in this subclone involved an internal deletion in the S_μ region of the expressed (switched) allele. One end of this deletion occurred very close to the switch recombination point. Despite the recombination-deletion mechanism of switching, the _γ2b-producing line retained two copies of the C_μ gene and two copies of the sequence just 5′ to the S_γ2b recombination point. The possible significance of the retention of these sequences to the mechanism of class switching is discussed.