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Related Experiment Videos

Human splenic IgM immunoglobulin transcripts are mutated at high frequency

R A Insel1, W S Varade, E Marin

  • 1Department of Pediatrics, Microbiology and Immunology, University of Rochester Medical Center, NY 14642.

Molecular Immunology
|April 1, 1994
PubMed
Summary

Human spleen B cells expressing IgM show high somatic hypermutation, suggesting they may function as memory B cells. These mutations indicate antigen selection, supporting a dissociation between mutation and isotype switching.

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Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • Somatic hypermutation is crucial for antibody diversification.
  • The role of IgM-expressing B cells as memory cells is debated.

Purpose of the Study:

  • To investigate the frequency and characteristics of somatic hypermutation in human spleen immunoglobulin gene rearrangements using the VH6 gene.
  • To determine if these mutations are antigenically selected.
  • To explore the potential of IgM+ B cells as human memory B cells.

Main Methods:

  • Polymerase chain reaction (PCR) amplification of spleen cDNA.
  • Restriction endonuclease analysis.
  • DNA sequencing of cloned immunoglobulin gene rearrangements.

Main Results:

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  • A high frequency of somatically mutated VH6 rearrangements was observed (3.1% mutation frequency).
  • Mutations were concentrated in complementarity determining regions (CDRs), suggesting antigenic selection.
  • Evidence of intraclonal diversification was found in some clones.
  • One donor showed lower mutation frequency and distribution, not indicative of selection.

Conclusions:

  • IgM-expressing B cells in the human spleen exhibit significant somatic hypermutation, consistent with antigen selection.
  • Findings support the dissociation of somatic hypermutation and isotype switching.
  • IgM+ B cells may serve as human memory B cells, contributing to adaptive immunity.