Cellular selection leads to age-dependent and reversible down-regulation of transgenic immunoglobulin light chain genes

International Immunology
S PetterssonM S Neuberger

Abstract

Analysis of immunoglobulin expression in mice transgenic for either a kappa light chain (driven by the kappa enhancer) or lambda light chain (driven by the IgH enhancer) revealed that the transgenic light chains are expressed by the majority of B lymphocytes in the neonatal mice. However, the proportion of B cells that express the transgenes at a detectable level decreases rapidly with age, with a concomitant increase in cells expressing rearrangements of one of the endogenous light chain loci. This appears to be the result of cellular selection. The down-regulation of transgene expression is not due to an irreversible mechanism as incubation of adult splenic lymphocytes with bacterial lipopolysaccharide leads to a rapid increase in the expression of the transgenic light chain on the B cell surface. In mice carrying the lambda transgene (but not in mice carrying the kappa transgene) the change with age in the pattern of transgene expression is accompanied by a shift towards B cells that do not express surface IgD. This shift towards IgM+/IgDlow B cells is also observed in mice transgenic for a chloramphenicol acetyltransferase gene linked to the IgH enhancer. This suggests that the down-regulation of IgD may either be due to th...Continue Reading

Citations

Oct 11, 1990·Nucleic Acids Research·K B MeyerM S Neuberger
Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·B Goyenechea, C Milstein
Jan 1, 1994·International Reviews of Immunology·B P Tsao, B H Hahn
Oct 1, 1996·European Journal of Immunology·T AnderssonS Pettersson
Jul 1, 1997·European Journal of Immunology·A GrandienA Coutinho
Jun 1, 1990·European Journal of Immunology·M J SharpeC Milstein
Jun 1, 1991·European Journal of Immunology·P DariavachM S Neuberger

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