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Recruiting memory B cells with changed antigenic specificity

J Ellenberger1, G Creadon, X Zhang

  • 1Division of Basic Sciences, National Jewish Center for Immunology and Respiratory Medicine, Denver CO 80206.

Journal of Immunology (Baltimore, Md. : 1950)
|November 15, 1993
PubMed
Summary
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Somatic hypermutation diversifies B cell receptors, enabling antibody responses. This study reveals that B cell mutations can lead to new specificities, expanding the antibody repertoire beyond initial antigen recognition.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • B lymphocytes undergo somatic hypermutation during T cell-dependent antibody responses.
  • Selection processes favor B cell clones with optimal antigen binding, obscuring unselected mutants.

Purpose of the Study:

  • To investigate whether unselected B cell mutants acquire new antigenic specificities.
  • To explore the generation of diverse antibody specificities from a single B cell clone.

Main Methods:

  • Mice were immunized with haptenated carrier proteins.
  • Booster injections with related haptens were administered during the primary immune response.
  • Hybridomas producing antibodies binding the second hapten but not the first were isolated and sequenced.

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Main Results:

  • V gene sequencing confirmed that some hybridomas derived from B cells with the original specificity had acquired a new specificity.
  • Identified B cell clones that lost original antigen specificity while gaining a new one.
  • Demonstrated recruitment of these mutants into the memory compartment via antigenic selection.

Conclusions:

  • B cell mutation can generate new antigenic specificities, not just improved binding to the original antigen.
  • In vivo selection processes reveal only a fraction of the mutationally diversified B cell clone.
  • A single B cell clone can give rise to antibodies with differing antigenic specificities.