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Somatic hypermutation in mouse lambda chains

T Azuma1

  • 1Division of Biosignalling, Science University of Tokyo, Chiba, Japan. tazuma@rs.noda.sut.ac.jp

Immunological Reviews
|May 29, 1998
PubMed
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Somatic hypermutation occurs frequently in active immunoglobulin genes but is protected in promoter regions. This process drives antibody affinity maturation, with specific mutations marking memory B cells during immunization.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Somatic hypermutation (SHM) is crucial for adaptive immunity, generating antibody diversity.
  • Understanding SHM's distribution and regulation is key to antibody engineering and autoimmune disease research.

Purpose of the Study:

  • To investigate the frequency and distribution of SHM in immunoglobulin genes.
  • To determine the impact of amino acid substitutions on antibody structure and function.
  • To explore the role of cis-acting elements in inducing SHM and identify memory B cell markers.

Main Methods:

  • Analysis of lambda 1 and lambda 2 immunoglobulin genes in anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) monoclonal antibodies.
  • Use of transgenic mice with chloramphenicol acetyl transferase reporter genes driven by immunoglobulin promoters/enhancers.

Related Experiment Videos

  • Characterization of memory B cells based on specific amino acid mutations (Trp to Leu at position 33).

    • Main Results:

    • High SHM frequency observed in V-J exons and J-C introns of active lambda 1 chains, with 5'-non-coding regions protected.
    • VH promoter and heavy-chain intron enhancer were found to induce SHM in both immunoglobulin and non-immunoglobulin genes.
    • Antibody affinity to NP increased up to 8,000-fold (affinity maturation), while fine specificity remained unchanged.
    • The Trp to Leu mutation at position 33, a memory B cell marker, was prevalent in early-stage hybridomas but rare in late-stage ones.

    Conclusions:

    • Specific regulatory elements protect promoter regions from SHM.
    • Cis-acting elements play a significant role in directing SHM.
    • Affinity maturation involves dynamic changes in the memory B cell population during immunization.