Light chain inclusion permits terminal B cell differentiation and does not necessarily result in autoreactivity

Proc Natl Acad Sci U S A. 2006 May 16;103(20):7747-52. doi: 10.1073/pnas.0509121103. Epub 2006 May 8.

Abstract

Mice in which the Jkappa cluster was replaced with a VkappaJkappa rearranged gene were studied. More than 90% of B cells from homozygous mutant mice expressed the transgenic kappa chain but showed a slightly reduced level of kappa transcripts compared with WT B lymphocytes. Light chain inclusion was apparent in 10% of B cells from these mice and raised 25% in hemizygous mice with a still lower expression of the knockin kappa chain. Beyond the rules of clonal selection, peripheral B cells developed in such animals, with included cells being activated and differentiating into class-switched or antibody-secreting cells. The high amount of included mature B cells was associated with an increase of hybrid kappa/lambda immunoglobulins but not with the increased prevalence of autoantibodies. Altogether, these data suggest that light chain exclusion prevalent in normal B cells mostly results from ordered rearrangements and stochastic mechanisms but is neither tightly ensured by a stringent cell selection process nor absolutely required for normal B cell function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / metabolism
  • B-Lymphocytes* / immunology
  • B-Lymphocytes* / physiology
  • Cell Differentiation / physiology*
  • Cell Lineage
  • Gene Rearrangement, B-Lymphocyte, Light Chain*
  • Humans
  • Hybridomas / immunology
  • Immunoglobulin Light Chains*
  • Immunoglobulin kappa-Chains / genetics
  • Immunoglobulin kappa-Chains / metabolism
  • Immunoglobulin lambda-Chains / genetics
  • Immunoglobulin lambda-Chains / metabolism
  • Mice
  • Mice, Transgenic
  • Multigene Family
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Spleen / cytology
  • Transgenes

Substances

  • Autoantibodies
  • Immunoglobulin Light Chains
  • Immunoglobulin kappa-Chains
  • Immunoglobulin lambda-Chains
  • Recombinant Fusion Proteins