Dmu expression causes enrichment of MZ B cells, but is non permissive for B cell maturation in Rag2-/- mice even if combined with Bcl-2

Mol Immunol. 2006 Mar;43(9):1316-24. doi: 10.1016/j.molimm.2005.09.020.

Abstract

Rearrangements in reading frame 2 promote the expression of a truncated heavy chain, the Dmu protein. Dmu can assemble into a pre-B cell receptor like complex that appears to induce a subset of signals elicited by full length mu, but cannot promote the pro-B to pre-B cell transition of Rag-/- B cells. In order to determine if this could stem from an impaired survival signal not properly induced by the Dmu protein, we introduced Bcl-2 into Dmu-transgenic, Rag2-/- mice. Despite the fact that the Bcl-2 transgene expression promoted some increase in the fraction of CD43- B cells, an identical increase was also observed in Rag2-/- mice. Moreover, whereas in mu-transgenic Rag2-/-Bcl-2+ mice, CD2 and CD25 expression were up regulated and c-Kit was down regulated, these markers were unaltered in Dmu-transgenic Rag2-/- Bcl-2+ mice compared to Rag2-/- Bcl-2+ mice, indicating that Dmu cannot support pre-B cell maturation despite extended survival of B cell precursors by Bcl-2. In addition, we observed that in Dmu-transgenic recombination competent mice, the Dmu induced partial block is permissive for marginal zone B cell development whereas the formation of follicular B cells is severely reduced. While the Dmu protein is expressed in peripheral B cells escaping the block, only a minor fraction of Dmu is exposed to the outer cell surface.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology*
  • Base Sequence
  • Cell Differentiation
  • DNA / genetics
  • DNA-Binding Proteins / deficiency*
  • DNA-Binding Proteins / genetics
  • Gene Expression
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, bcl-2*
  • Humans
  • Immunoglobulin mu-Chains / genetics*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic

Substances

  • DNA-Binding Proteins
  • Immunoglobulin mu-Chains
  • Rag2 protein, mouse
  • DNA