UMMS Affiliation

Department of Molecular Genetics and Microbiology

Publication Date

2002-02-04

Document Type

Article

Subjects

Adenosine Triphosphatases; Animals; B-Lymphocytes; *Base Pair Mismatch; Base Sequence; Carrier Proteins; DNA; DNA Repair; *DNA Repair Enzymes; DNA-Binding Proteins; *Immunoglobulin Class Switching; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Sequence Data; MutS Homolog 2 Protein; Neoplasm Proteins; Nuclear Proteins; Proto-Oncogene Proteins; Recombination, Genetic; Sequence Homology, Nucleic Acid

Disciplines

Life Sciences | Medicine and Health Sciences | Women's Studies

Abstract

B cells from mice deficient in mismatch repair (MMR) proteins show decreased ability to undergo class switch recombination in vitro and in vivo. The deficit is not accompanied by any reduction in cell viability or alterations in the cell cycle in B cells cultured in vitro. To assess the role of MMR in switching we examined the nucleotide sequences of Smicro-Sgamma3 recombination junctions in splenic B cells induced in culture to switch to IgG3. The data demonstrate clear differences in the sequences of switch junctions in wild-type B cells in comparison with Msh2-, Mlh1-, and Pms2-deficient B cells. Sequences of switch junctions from Msh2-deficient cells showed decreased lengths of microhomology between Smicro and Sgamma3 relative to junctions from wild-type cells and an increase in insertions, i.e., nucleotides which do not appear to be derived from either the Smicro or Sgamma3 parental sequence. By contrast, 23% of junctions from Mlh1- and Pms2-deficient cells occurred at unusually long stretches of microhomology. The data indicate that MMR proteins are directly involved in class switching and that the role of Msh2 differs from that of Mlh1 and Pms2.

Keywords

splenic B cells, DNA recombination, DNA repair, antibody heavy chain isotypes, mismatch repair

Rights and Permissions

Publisher PDF posted as allowed by the publisher's terms of use policy at: http://www.rupress.org/terms. After the Initial Publication Period, RUP will grant to the public the non-exclusive right to copy, distribute, or display the Article under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode, or updates thereof.

DOI of Published Version

10.1084/jem.20011877

Source

J Exp Med. 2002 Feb 4;195(3):367-73.

Journal/Book/Conference Title

The Journal of experimental medicine

Related Resources

Link to article in PubMed

PubMed ID

11828012

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.

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