Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization

Nature. 1999 Aug 12;400(6745):682-7. doi: 10.1038/23287.

Abstract

Models of B-cell development in the immune system suggest that only those immature B cells in the bone marrow that undergo receptor editing express V(D)J-recombination-activating genes (RAGs). Here we investigate the regulation of RAG expression in transgenic mice carrying a bacterial artificial chromosome that encodes a green fluorescent protein reporter instead of RAG2. We find that the reporter is expressed in all immature B cells in the bone marrow and spleen. Endogenous RAG messenger RNA is expressed in immature B cells in bone marrow and spleen and decreases by two orders of magnitude as they acquire higher levels of surface immunoglobulin M (IgM). Once RAG expression is stopped it is not re-induced during immune responses. Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate allelic exclusion, receptor editing and tolerance.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / transplantation
  • Bone Marrow Cells / cytology
  • Cell Differentiation
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation, Enzymologic*
  • Gene Rearrangement, B-Lymphocyte
  • Germinal Center / cytology
  • Green Fluorescent Proteins
  • Immunoglobulin M / biosynthesis
  • Interleukin-4 / immunology
  • Leukopoiesis / physiology
  • Lipopolysaccharides / immunology
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Transgenic
  • RNA, Messenger / metabolism
  • Spleen / cytology

Substances

  • DNA-Binding Proteins
  • Immunoglobulin M
  • Lipopolysaccharides
  • Luminescent Proteins
  • RNA, Messenger
  • Rag2 protein, mouse
  • V(D)J recombination activating protein 2
  • Green Fluorescent Proteins
  • Interleukin-4