Activated Ras signals developmental progression of recombinase-activating gene (RAG)-deficient pro-B lymphocytes

J Exp Med. 1999 Jan 4;189(1):123-9. doi: 10.1084/jem.189.1.123.

Abstract

To elucidate the intracellular pathways that mediate early B cell development, we directed expression of activated Ras to the B cell lineage in the context of the recombination-activating gene 1 (RAG1)-deficient background (referred to as Ras-RAG). Similar to the effects of an immunoglobulin (Ig) mu heavy chain (HC) transgene, activated Ras caused progression of RAG1-deficient progenitor (pro)-B cells to cells that shared many characteristics with precursor (pre)-B cells, including downregulation of surface CD43 expression plus expression of lambda5, RAG2, and germline kappa locus transcripts. However, these Ras-RAG pre-B cells also upregulated surface markers characteristic of more mature B cell stages and populated peripheral lymphoid tissues, with an overall phenotype reminiscent of B lineage cells generated in a RAG- deficient background as a result of expression of an Ig mu HC together with a Bcl-2 transgene. Taken together, these findings suggest that activated Ras signaling in pro-B cells induces developmental progression by activating both differentiation and survival signals.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • Cell Differentiation / genetics
  • Cell Survival / genetics
  • DNA-Binding Proteins / genetics
  • Enzyme Activation / genetics*
  • Gene Expression Regulation, Developmental / genetics
  • Genes, RAG-1 / genetics*
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin kappa-Chains / genetics
  • Mice
  • Mice, Knockout
  • Phenotype
  • RNA, Messenger / genetics
  • Stem Cells / metabolism
  • Transcription, Genetic / genetics
  • Up-Regulation / genetics
  • ras Proteins / genetics*

Substances

  • DNA-Binding Proteins
  • Immunoglobulin Heavy Chains
  • Immunoglobulin kappa-Chains
  • RNA, Messenger
  • Rag2 protein, mouse
  • V(D)J recombination activating protein 2
  • ras Proteins