UMMS Affiliation

Department of Molecular Genetics and Microbiology

Publication Date

1999-08-02

Document Type

Article

Subjects

*Adenosine Triphosphatases; Animals; B-Lymphocytes; Base Pair Mismatch; Carrier Proteins; Cell Cycle; Cell Division; Cell Survival; Cells, Cultured; DNA Repair; *DNA Repair Enzymes; *DNA-Binding Proteins; Flow Cytometry; Immunoglobulin Class Switching; Immunoglobulin Isotypes; Mice; Neoplasm Proteins; Nuclear Proteins; Proteins; Spleen

Disciplines

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

Abstract

Mice deficient in various mismatch repair (MMR) enzymes were examined to determine whether this repair pathway is involved in antibody class switch recombination. Splenic B cells from mice deficient in Msh2, Mlh1, Pms2, or Mlh1 and Pms2 were stimulated in culture with lipopolysaccharide (LPS) to induce immunoglobulin (Ig)G2b and IgG3, LPS and interleukin (IL)-4 to induce IgG1, or LPS, anti-delta-dextran, IL-4, IL-5, and transforming growth factor (TGF)-beta1 to induce IgA. After 4 d in culture, cells were surface stained for IgM and non-IgM isotypes and analyzed by FACS((R)). B cells from MMR-deficient mice show a 35-75% reduction in isotype switching, depending on the isotype and on the particular MMR enzyme missing. IgG2b is the most affected, reduced by 75% in Mlh1-deficient animals. The switching defect is not due to a lack of maturation of the B cells, as purified IgM(+)IgD(+) B cells show the same reduction. MMR deficiency had no effect on cell proliferation, viability, or apoptosis, as detected by [(3)H]thymidine incorporation and by propidium iodide staining. The reduction in isotype switching was demonstrated to be at the level of DNA recombination by digestion-circularization polymerase chain reaction (DC-PCR). A model of the potential role for MMR enzymes in class switch recombination is presented.

Keywords

class switch recombination, msh2, mlh1, pms2

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.190.3.323

Source

J Exp Med. 1999 Aug 2;190(3):323-30.

Journal/Book/Conference Title

The Journal of experimental medicine

Related Resources

Link to article in PubMed

PubMed ID

10430621

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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