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Related Experiment Videos

Developmental changes in the human heavy chain CDR3.

M Margarida Souto-Carneiro1, Gary P Sims, Hermann Girschik

  • 1Repertoire Analysis Group, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1820, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|November 23, 2005
PubMed
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Fetal B cells have shorter immunoglobulin heavy chain CDR3 regions due to less TdT enzyme activity and preferential use of specific D segments. These features contribute to developmental changes in the B cell repertoire during ontogeny.

Area of Science:

  • Immunology
  • Developmental Biology
  • Molecular Genetics

Background:

  • The complementarity-determining region 3 (CDR3) of the immunoglobulin heavy (Ig H) chain exhibits distinct characteristics in fetal versus adult B cell repertoires.
  • Understanding the molecular mechanisms driving these developmental changes is crucial for comprehending B cell maturation.

Purpose of the Study:

  • To investigate the mechanisms underlying developmental alterations in the CDR3(H) repertoire.
  • To compare nonproductive and productive V(H)DJ(H) rearrangements in fetal and adult B cells to identify selection-independent changes.

Main Methods:

  • Analysis of nonproductive V(H)DJ(H) rearrangements from fetal, neonatal, and adult single B cells.
  • Comparison of nonproductive rearrangements with corresponding productive repertoires.

Related Experiment Videos

  • Assessment of TdT activity, D segment usage (specifically D7-27), DJ(H) rearrangements, and junctional microhomology usage.

    • Main Results:

    • Fetal B cells exhibit shorter CDR3(H) primarily due to diminished TdT activity and preferential use of the proximal D segment D7-27.
    • The enhanced usage of D7-27 in fetal cells is linked to its locus position rather than its length.
    • Fetal B cells show decreased recurrent DJ(H) rearrangements and increased junctional microhomology usage compared to adults, with these patterns shifting during ontogeny.

    Conclusions:

    • The shorter length and reduced complexity of fetal CDR3(H) result from limited enzymatic modifications and a preference for proximal D and J(H) segments during V(H)DJ(H) recombination.
    • These findings highlight key molecular events driving the maturation of the B cell repertoire from fetal to adult stages.