Loss of lambda2(315) transgene copy numbers influences the development of B1 cells

Mol Immunol. 2009 Apr;46(7):1542-50. doi: 10.1016/j.molimm.2008.12.024. Epub 2009 Feb 10.

Abstract

Transgenic L2 mice contain high numbers of the lambda2(315) immunoglobulin L chain gene in their germ line. They are characterized by an almost complete block in B2 cell development and dominance of B1 cells in their periphery. This was attributed to high transgene expression. Here, we describe a variant of such mice (L2V), which has lost half of the transgene copies. This results in decreased transgene expression. Consequently, such mice display less severe isotype exclusion and an increase in B cells expressing endogenous kappa light chains. In addition, the B2 cell compartment is enlarged. Nevertheless, L2V mice exhibit phosphatidylcholine (PtC) binding B cells expressing lambda L chains as well as an unaltered number of B1a cells expressing the dominating specificity usually encountered in L2 mice. Since in L2V mice transgene integration and regulation is identical to L2 mice, the correlation of decreased transgene expression and increased presence of B2 cells strongly suggests that high transgene expression is decisive for development of B1 cells in L2 mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / physiology*
  • Cell Differentiation / genetics*
  • Gene Deletion
  • Gene Dosage / physiology*
  • Gene Expression
  • Immunoglobulin lambda-Chains / blood
  • Immunoglobulin lambda-Chains / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Mutant Proteins / blood
  • Mutant Proteins / genetics
  • Rats
  • Transgenes / physiology*
  • Tumor Cells, Cultured

Substances

  • Immunoglobulin lambda-Chains
  • Mutant Proteins