The Ig(kappa) enhancer influences the ratio of Ig(kappa) versus Ig(lambda) B lymphocytes

Immunity. 1996 Sep;5(3):241-52. doi: 10.1016/s1074-7613(00)80319-2.

Abstract

We generated mice harboring germline mutations in which the enhancer element located 9 kb 3' of the immunoglobulin kappa light chain gene (3'E kappa) was replaced either by a single loxP site (3'E kappa delta) or by a neomycin resistance gene (3'E kappa N). Mice homozygous for the 3'E(kappa delta) mutation had substantially reduced numbers of kappa-expressing B cells and increased numbers of lambda-expressing B cells accompanied by decreased kappa versus lambda gene rearrangement. In these mutant mice, kappa expression was reduced in resting B cells, but was normal in activated B cells. The homozygous 3'E(kappa)N mutation resulted in a similar but more pronounced phenotype. Both mutations acted in cis. These studies show that the 3'E(kappa) is critical for establishing the normal kappa/lambda ratio, but is not absolutely essential for kappa gene rearrangement or, surprisingly, for normal kappa expression in activated B cells. These studies also imply the existence of additional regulatory elements that have overlapping function with the 3'E(kappa) element.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Enhancer Elements, Genetic / physiology*
  • Female
  • Gene Rearrangement
  • Genes, Immunoglobulin*
  • Immunoglobulin kappa-Chains / genetics*
  • Immunoglobulin lambda-Chains / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mutation

Substances

  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains