Constitutive expression of terminal deoxynucleotidyl transferase in transgenic mice is sufficient for N region diversity to occur at any Ig locus throughout B cell differentiation

J Immunol. 1997 Jan 15;158(2):715-23.

Abstract

N region diversity in Ag receptors is a developmentally regulated process in B and T cells that correlates with the differential expression of terminal deoxynucleotidyl transferase (TdT). Absent in fetal and newborn mice, TdT expression is restricted to early T and pro-B cells in adults. To extend the TdT expression pattern throughout B cell ontogenesis, we generated transgenic mice carrying a TdT cDNA under the regulatory elements of the N-myc gene and the IgH enhancer. High expression was observed in secondary lymphoid organs consistent with TdT activity beyond the pre-B cell stage. This suggests that TdT transgene expression is not down-regulated as is the endogenous gene. Unlike normal mice, extensive N region diversity was found in rearranged lambda light chain genes of adult transgenic animals. Therefore, expression of TdT appears sufficient for N region diversity to occur at any Ig locus. More importantly, expression of the transgene takes place during fetal development. As a consequence, the potential fetal B cell repertoire is modified as both rearranged heavy and light chain genes now show N region additions. Constitutive expression of TdT throughout B cell differentiation does not therefore appear deleterious and suggests that TdT is recruited only to participate in the V(D)J recombination process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Diversity / genetics*
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology*
  • Base Composition
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • DNA Nucleotidylexotransferase / biosynthesis*
  • Gene Rearrangement / immunology*
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Variable Region / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Sequence Homology, Nucleic Acid
  • Transfection

Substances

  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region
  • DNA Nucleotidylexotransferase