Immunoglobulin (Ig) heavy chain (HC) class switch recombination (CSR) is a late B cell process that involves intrachromosomal DNA rearrangement. Ku70 and Ku80 form a DNA end-binding complex required for DNA double strand break repair and V(D)J recombination. Ku70−/− (K70T) mice, like recombination activating gene (RAG)-1– or RAG-2–deficient (R1T or R2T) mice, have impaired B and T cell development at an early progenitor stage, which is thought to result at least in part from defective V(D)J recombination (Gu, Y., K.J. Seidl, G.A. Rathbun, C. Zhu, J.P. Manis, N. van der Stoep, L. Davidson, H.L. Cheng, J.M. Sekiguchi, K. Frank, et al. 1997. Immunity. 7:653–665; Ouyang, H., A. Nussenzweig, A. Kurimasa, V.C. Soares, X. Li, C. Cordon-Cardo, W. Li, N. Cheong, M. Nussenzweig, G. Iliakis, et al. 1997. J. Exp. Med. 186:921–929). Therefore, to examine the potential role of Ku70 in CSR, we generated K70T mice that carry a germline Ig HC locus in which the JH region was replaced with a functionally rearranged VH(D)JH and Ig λ light chain transgene (referred to as K70T/HL mice). Previously, we have shown that B cells from R1T or R2T mice carrying these rearranged Ig genes (R1T/HL or R2T/HL mice) can undergo CSR to IgG isotypes (Lansford, R., J. Manis, E. Sonoda, K. Rajewsky, and F. Alt. 1998. Int. Immunol. 10:325–332). K70T/HL mice had significant numbers of peripheral surface IgM+ B cells, which generated serum IgM levels similar to those of R2T/HL mice. However, in contrast to R2T/HL mice, K70T/HL mice had no detectable serum IgG isotypes. In vitro culture of K70T/HL B cells with agents that induce CSR in normal or R2T/HL B cells did lead to the induction of germline CH transcripts, indicating that initial signaling pathways for CSR were intact in K70T/HL cells. However, treatment with such agents did not lead to detectable CSR by K70T/HL B cells, and instead, led to cell death within 72 h. We conclude that Ku70 is required for the generation of B cells that have undergone Ig HC class switching. Potential roles for Ku70 in the CSR process are discussed.
Skip Nav Destination
Article navigation
15 June 1998
Article|
June 15 1998
Ku70 Is Required for Late B Cell Development and Immunoglobulin Heavy Chain Class Switching
John P. Manis,
John P. Manis
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Search for other works by this author on:
Yansong Gu,
Yansong Gu
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Search for other works by this author on:
Rusty Lansford,
Rusty Lansford
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Search for other works by this author on:
Eiichiro Sonoda,
Eiichiro Sonoda
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Search for other works by this author on:
Roger Ferrini,
Roger Ferrini
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Search for other works by this author on:
Laurie Davidson,
Laurie Davidson
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Search for other works by this author on:
Klaus Rajewsky,
Klaus Rajewsky
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Search for other works by this author on:
Frederick W. Alt
Frederick W. Alt
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Search for other works by this author on:
John P. Manis
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Yansong Gu
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Rusty Lansford
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Eiichiro Sonoda
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Roger Ferrini
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Laurie Davidson
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Klaus Rajewsky
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Frederick W. Alt
From the *Howard Hughes Medical Institute, Boston, Massachusetts 02115; the ‡Children's Hospital, Boston, Massachusetts 02115; the §Center for Blood Research and the ‖Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115; the ¶Department of Molecular Immunology and Allergy, Kyoto University, Kyoto 606-01, Japan; and the **Institute for Genetics, University of Cologne, 5000 Cologne 41, Germany
Address correspondence to Frederick W. Alt, The Howard Hughes Medical Institute, The Children's Hospital, 861, 320 Longwood Ave., Boston, MA 02115. Phone: 617-355-7290; Fax: 617-730-0432; E-mail: [email protected]
R. Lansford's current address is Division of Biology, California Institute of Technology, Pasadena, CA 91125.
Received:
March 19 1998
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1998
J Exp Med (1998) 187 (12): 2081–2089.
Article history
Received:
March 19 1998
Citation
John P. Manis, Yansong Gu, Rusty Lansford, Eiichiro Sonoda, Roger Ferrini, Laurie Davidson, Klaus Rajewsky, Frederick W. Alt; Ku70 Is Required for Late B Cell Development and Immunoglobulin Heavy Chain Class Switching . J Exp Med 15 June 1998; 187 (12): 2081–2089. doi: https://doi.org/10.1084/jem.187.12.2081
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement
