Ontogeny of the heavy chain immunoglobulin repertoire in fetal liver and bone marrow

J Immunol. 1998 Apr 1;160(7):3274-80.

Abstract

We studied the kinetics of maturation of B cell progenitors in the mouse embryo, from day 15 of development to birth, both in liver and bone marrow. The analysis of Ig heavy chain rearrangements at different time points of late fetal development shows that oligoclonal patterns of V(H)-D-J(H) rearrangements are detected by day 15 in fetal liver. The pattern is polyclonal and diverse by day 17; however, 80% of the rearrangements are nonproductive. In bone marrow, the pattern of rearrangements is less diverse at birth, although the percentage of nonproductive rearrangements approaches adult bone marrow levels (35-40%). After day 17 in fetal liver, there is a sudden reversal in the percentage of nonproductive rearrangements that reaches 33% at day 19 (birth). Maturation of B cells, as measured by the fraction of surface Ig+ in total B220+ cells and the presence of N sequence additions in V(H)-D-J(H) joints, occurs in the marrow before fetal liver. These results demonstrate that the lymphopoietic environment in fetal liver and bone marrow of animals at the same stage of development is functionally distinct.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Embryonic and Fetal Development / genetics
  • Embryonic and Fetal Development / immunology*
  • Flow Cytometry
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, Immunoglobulin*
  • Immunoglobulin Heavy Chains / analysis
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Joining Region / genetics
  • Immunoglobulin Variable Region / genetics
  • Liver / cytology
  • Liver / immunology*
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Sequence Analysis, DNA
  • Stem Cells / metabolism

Substances

  • Immunoglobulin Heavy Chains
  • Immunoglobulin Joining Region
  • Immunoglobulin Variable Region