Isotype exclusion in λ1 transgenic mice depends on transgene copy number and diminishes with down‐regulation of transgene transcripts

摘要

AbstractWe have compared expression of the endogenous χ and transgenic λ1 light chains in three lines of mice carrying one, four and eight copies of a λ1 transgene. We have found that in very young mice, even a single rearranged transgenic λ allele excludes expression of the endogenous χ loci. As the λ1 transgenic mice age, the proportion of λ‐positive cells decreases, as has been reported by others (Neuberger et al.,Nature1989.338:350; Pettersson et al.,Nature1990.344:165; Hagman et al.,J. Exp. Med.1989.169:1911; Bogen and Weiss,Eur. J. Immunol.1991.21:2391). The decrease in λ‐positive B cells is accompanied by an increase in χ‐positive cells. We show that the decrease in B cells bearing surface λ immunoglobulin depends on transgene copy number and occurs most rapidly in lower copy number lines. The decrease in surface λ expression correlates with a dramatic decrease in the level of λ mRNA in splenic B cells. Transgene down‐regulation cannot be alleviated by stimulation of splenocytes with the mitogen lipopolysaccharide. These are the first data to establish that a single copy transgene can effect isotype exclusion. In addition, these results provide strong evidence that down‐regulation of transgene expression is controlled at the level of transcription, and that it is the level of expressed light chain that regula