Sequences of immunoglobulin λ1 genes in a λ1 defective mouse strain

Abstract

The λ1 light chain accounts for about 80% of λ immunoglobulin chains in BALB/c mice, the remainder being λ2 and λ3 (refs 1, 2). Several inbred strains of mice, most notably the SJL strain, have greatly reduced λ1 expression compared with other strains. Genetic analysis of SJL mice indicates there is a cis-acting defect linked to the λ1 structural gene³. Although this defect reduces both the number of spleen cells expressing surface λ1 and the serum level of λ1, the λ1 antibodies that are produced appear normal³. A possible explanation for such a defect would be an alteration of the recognition sequences involved in the rearrangement of the variable (V) and constant (C) region genes for λ1. However, the defect could reside in other structural elements involving transcription, RNA processing, protein chain folding or light and heavy chain association. Furthermore, a more general regulatory defect must be considered, as SJL mice also appear somewhat depressed in the synthesis of λ2 chains^1,3,4. As a first approach to the analysis of the genetic defect in SJL mice, we have now analysed the structural genes involved in the formation of λ1 chains and have found one change leading to an amino acid replacement in the exon of Cλ1. Whether this alteration is of functional significance remains to be elucidated; however, analysis of the DNA of several mouse strains confirms on the molecular level that the SJL defect is closely linked to the λ locus.