Isotype exclusion and transgene down-regulation in immunoglobulin-λ transgenic mice

摘要: A GIVEN B lymphocyte makes an antibody containing either κ-or λ-light chains, but not both1,2. This isotype exclusion is effected at the level of rearrangement immunoglobulin gene segments3–5, although by unknown mechanism. An attractive possibility that, following productive one light-chain loci, newly synthesized polypeptide inhibits DNA for other isotype. To test such feedback regulation, we have created transgenic mice carrying a rearranged λ1-gene. By contrast with cells in normal newborn which are mainly κ+λ−, express λ- κ-chains. We propose that synthesis any light chain, be it κ or λ, allows expression IgM on cell surface results cessation all V–J joining. Interestingly, limited repertoire does persist and most adult endogenous κ-rearrangements down-regulate transgene.