Ku70 is required for late B cell development and immunoglobulin heavy chain class switching

Journal of Experimental Medicine

Volumn 187, Issue 12, 1998, Pages 2081-2089

  Manis, John P ^a,b,d   Gu, Yansong ^a,b,d   Lansford, Rusty ^c   Sonoda, Eiichiro ^e   Ferrini, Roger ^a,b   Davidson, Laurie ^a,b   Rajewsky, Klaus ^f   Alt, Frederick W ^a,b,c,d  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

^c CENTER FOR BLOOD RESEARCH   (United States)

^d HARVARD MEDICAL SCHOOL   (United States)

^e KYOTO UNIVERSITY   (Japan)

^f UNIVERSITY OF COLOGNE   (Germany)

Author keywords

B cell development; Immunoglobulin class switch recombination; Ku70; Recombination activating gene 2

Indexed keywords

IMMUNOGLOBULIN CLASS; IMMUNOGLOBULIN HEAVY CHAIN; IMMUNOGLOBULIN LIGHT CHAIN; IMMUNOGLOBULIN M;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; B LYMPHOCYTE; CELL MATURATION; DNA REPAIR; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; GENE REARRANGEMENT; MOUSE; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; SPLEEN CELL; TRANSGENE;

ANIMALS; ANTIGENS, NUCLEAR; B-LYMPHOCYTES; DNA HELICASES; DNA-BINDING PROTEINS; HEMATOPOIETIC STEM CELLS; IMMUNOGLOBULIN CLASS SWITCHING; IMMUNOGLOBULIN G; IMMUNOGLOBULIN HEAVY CHAINS; IMMUNOGLOBULIN ISOTYPES; IMMUNOGLOBULIN LIGHT CHAINS; MICE; MICE, MUTANT STRAINS; MICE, TRANSGENIC; NUCLEAR PROTEINS; RECOMBINATION, GENETIC;

EID: 0032526290     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.187.12.2081     Document Type: Article

References (63)

1. Tonegawa, S. 1983. Somatic generation of antibody diversity. Nature. 302:575-581.
2. Willerford, D.M., W. Swat, and F.W. Alt. 1996. Developmental regulation of V(D)J recombination and lymphocyte differentiation. Curr. Opin. Genet. Dev. 6:603-609.
3. Jin, S., S. Inoue, and D.T. Weaver. 1997. Functions of the DNA dependent protein kinase. Cancer Surv. 29:221-261.
4. Lansford, R., J. Chen, E. Oltz, T.K. Blackwell, F.W. Alt, and G. Rathbun. 1996. Mechanism and control of immunoglobulin gene rearrangement. In Molecular Immunology. D.B. Hames and D.M. Glover, editors. Oxford University Press, Oxford. 248-282.
5. Zhang, J., F. W. Alt, and T. Honjo. 1995. Regulation of class switch recombination of the immunoglobulin heavy chain genes. In Immunoglobuhn Genes, 2nd ed. T. Honjo and F.W. Alt, editors. Academic Press Limited, London. 235-265.
6. Finkelman, F.D., J. Holmes, I.M. Katona, J.F. Urban, Jr., M.P. Beckmann, L.S. Park, K.A. Schooley, R.L. Coffman, T.R. Mosmann, and W.E. Paul. 1990. Lymphokine control of in vivo immunoglobulin isotype selection. Annu. Rev. Immunol. 8:303-333.
7. Bottaro, A., and F.W. Alt. 1997. Local and general control elements of immunoglobulin class switch recombination. In IgE Regulation: Molecular Mechanisms. D. Vercelli, editor. John Wiley & Sons Ltd., London. 155-177.
8. Snapper, C.M., K.B. Marcu, and P. Zelazowski. 1997. The immunoglobulin class switch: beyond "accessibility." Immunity. 6:217-223.
9. von Schwedler, U., H.M. Jack, and M. Wabl. 1990. Circular DNA is a product of the immunoglobulin class switch rearrangement. Nature. 345:452-456.
10. Matsuoka, M., K. Yoshida, T. Maeda, S. Usuda, and H. Sakano. 1990. Switch circular DNA formed in cytokine-treated mouse splenocytes: evidence for intramolecular DNA deletion in immunoglobulin class switching. Cell. 62:135-142.
11. Iwasato, T., A. Shimizu, T. Honjo, and H. Yamagishi. 1990. Circular DNA is excised by immunoglobulin class switch recombination. Cell. 62:143-149.
12. Dunnick, W., G.Z. Hertz, L. Scappino, and C. Gritzmacher. 1993. DNA sequences at immunoglobulin switch region recombination sites. Nucleic Acids Res. 21:365-372.
13. Stavnezer, J. 1996. Immunoglobulin class switching. Curr. Opin. Immunol. 8:199-205.
14. Wuerffel, R.A., J. Du, R.J. Thompson, and A.L. Kenter. 1997. Ig Sγ3 DNA-specific double strand breaks are induced in mitogen-activated B cells and are implicated in switch recombination. J. Immunol. 159:4139-4144.
15. Jeggo, P.A., G.E. Taccioli, and S.P. Jackson. 1995. Menage a trois: double strand break repair. V(D)J recombination and DNA-PK. Bioessays. 17:949-957.
16. Taccioli, G.E., G. Rathbun, E. Oltz, T. Stamato, P.A. Jeggo, and F.W. Alt. 1993. Impairment of V(D)J recombination in double-strand break repair mutants. Science. 260:207-210.
17. Gottlieb, T.M., and S.P. Jackson. 1993. The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell. 72:131-142.
18. Danska, J.S., D.P. Holland, S. Mariathasan, K.M. Williams, and C.J. Guidos. 1996. Biochemical and genetic detects in the DNA-dependent protein kinase in murine scid lymphocytes. Mol. Cell. Biol. 16:5507-5517.
19. Blunt, T., D. Gell, M. Fox, G.E. Taccioli, A.R. Lehmann, S.P. Jackson, and P.A. Jeggo. 1996. Identification of a non-sense mutation in the carboxyl-termmal region of DNA-dependent protein kinase catalytic subunit in the scid mouse. Proc. Natl. Acad. Sci. USA. 93:10285-10290.
20. Bosma, G.C., R.P. Custer, and M.J. Bosma. 1983. A severe combined immunodeficiency mutation in the mouse. Nature. 301:527-530.
21. Blackwell, T.K., B.A. Malynn, R.R. Pollock, P. Ferrier, L.R. Covey, G.M. Fulop, R.A. Phillips, G.D. Yancopoulos, and F.W. Alt. 1989. Isolation of scid pre-B cells that rearrange kappa light chain genes: formation of normal signal and abnormal coding joins. EMBO (Eur. Mol. Biol. Organ.) J. 8: 735-742.
22. Ferrier, P., L.R. Covey, S.C. Li, H. Suh, B.A. Malynn, T.K. Blackwell, M.A. Morrow, and F.W. Alt. 1990. Normal recombination substrate VH to DJH rearrangements in pre-B cell lines from scid mice. J. Exp. Med. 171:1909-1918.
23. Lieber, M.R., J.E. Hesse, S. Lewis, G.C. Bosma, N. Rosenberg, K. Mizuuchi, M.J. Bosma, and M. Gellert. 1988. The detect in murine severe combined immune deficiency: joining of signal sequences but not coding segments in V(D)J recombination. Cell. 55:7-16.
24. Malynn, B.A., T.K. Blackwell, G.M. Fulop, G.A. Rathbun, A.J. Furley, P. Ferrier, L.B. Heinke, R.A. Phillips, G.D. Yancopoulos, and F.W. Alt. 1988. The scid defect affects the final step of the immunoglobulin VDJ recombinase mechanism. Cell. 54:453-460.
25. Rolink, A., F. Melchers, and J. Andersson. 1996. The SCID but not the RAG-2 gene product is required for Sμ-S∈ heavy chain class switching. Immunity. 5:319-330.
26. Carroll, A.M., R.R. Hardy, and M.J. Bosma. 1989. Occurrence of mature B (IgM+, B220+) and T (CD3+) lymphocytes in scid mice. J. Immunol. 143:1087-1093.
27. 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. Growth retardation and leaky SCID phenotype of Ku70-deficient mice. Immunity. 7:653-665.
28. Gu, Y., S. Jin, Y. Gao, D.T. Weaver, and F.W. Alt. 1997. Ku70-deficient embryonic stem cells have increased ionizing radiosensitivity, defective DNA end-binding activity, and inability to support V(D)J recombination. Proc. Natl. Acad. Sci. USA. 94:8076-8081.
29. 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. Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination in vivo. J. Exp. Med. 186:921-929.
30. Zhu, C., M.A. Bogue, D.S. Lim, P. Hasty, and D.B. Roth. 1996. Ku86-deficient mice exhibit severe combined immunodeficiency and defective processing of V(D)J recombination intermediates. Cell. 86:379-389.
31. Nussenzweig, A., C. Chen., V. da Costa Soares, M. Sanchez, K. Sokol, M.C. Nussenzweig, and G.G. Li. 1996. Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature. 382:551-555.
32. Nussenzweig, A., K. Sokol, P. Burgman, L. Li, and G.C. Li. 1997. Hypersensitivity of Ku80-deficient cell lines and mice to DNA damage: the effects of ionizing radiation on growth, survival, and development. Proc. Natl. Acad. Sci. USA. 94: 13588-13593.
33. Lansford, R., J. Manis, E. Sonoda, K. Rajewsky, and F. Alt. 1998. Ig heavy chain class switching in rag-deficient mice. Int. Immunol. 10:325-332.
34. Sonoda, E., Y. Pewzner-Jung, S. Schwers, S. Taki, S. Jung, D. Eilat, and K. Rajewsky. 1997. B cell development under the condition of allelic inclusion. Immunity. 6:225-233.
35. Young, F., B. Ardman, Y. Shinkai, R. Lansford, T.K. Blackwell, M. Mendelsohn, A. Rolink, F. Melchers, and F.W. Alt. 1994. Influence of immunoglobuhn heavy-and light-chain expression on B-cell differentiation. Genes Dev. 8:1043-1057.
36. Shinkai, Y., G. Rathbun, K.P. Lam, E.M. Oltz, V. Stewart, M. Mendelsohn, J. Charron, M. Datta, F. Young, A.M. Stall, et al. 1992. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 68: 855-867.
37. Bottaro, A., R. Lansford., L. Xu, J. Zhang, P. Rothman, and F.W. Alt. 1994. S region transcription per se promotes basal IgE class switch recombination but additional factors regulate the efficiency of the process. EMBO (Eur. Mol. Biol. Organ.) J. 13:665-674.
38. Cogne, M., R. Lansford, A. Bottaro, J. Zhang, J. Gorman, F. Young, H.L. Cheng, and F.W. Alt. 1994. A class switch control region at the 3′ end of the immunoglobulin heavy chain locus. Cell. 77:737-747.
39. Zelazowski, P., D. Carrasco, F.R. Rosas, M.A. Moorman, R. Bravo, and C.M. Snapper. 1997. B cells genetically deficient in the c-Rel transactivation domain have selective defects in germline CH transcription and Ig class switching. J. Immunol. 159:3133-3139.
40. Chu, C.C., E.E. Max, and W.E. Paul. 1993. DNA rearrangement can account for in vitro switching to IgG1. J. Exp. Med. 178:1381-1390.
41. Chang, Y., G.C. Bosma, and M.J. Bosma. 1995. Development of B cells in scid mice with immunoglobulin transgenes: implications for the control of V(D)J recombination. Immunity. 2:607-616.
42. Reichman-Fried, M., R.R. Hardy, and M.J. Bosma. 1990. Development of B-lineage cells in the bone marrow of scid/ scid mice following the introduction of functionally rearranged immunoglobulin transgenes. Proc. Natl. Acad. Sci. USA. 87:2730-2734.
43. Snapper, C.M., P. Zelazowski, F.R. Rosas, M.R. Kehry, M. Tian, D. Baltimore, and W.C. Sha. 1996. B cells from p50/ NF-κB knockout mice have selective defects in proliferation, differentiation, germ-line CH transcription, and Ig class switching. J. Immunol. 156:183-191.
44. Han, S., B. Zheng, D.G. Schatz, E. Spanopoulou, and G. Kelsoe. 1996. Neoteny in lymphocytes: Rag1 and Rag2 expression in germinal center B cells. Science. 274:2094-2097.
45. Hikida, M., M. Mori, T. Takai, K. Tomochika, K. Hamatani, and H. Ohmori. 1996. Reexpression of RAG-1 and RAG-2 genes in activated mature mouse B cells. Science. 274: 2092-2094.
46. Papavasiliou, F., R. Casellas, H. Suh, X.F. Qin, E. Besmer, R. Pelanda, D. Nemazee, K. Rajewsky, and M.C. Nussenzweig. 1997. V(D)J recombination in mature B cells: a mechanism for altering antibody responses. Science. 278:298-301.
47. Han, S., S.R. Dillon, B. Zheng, M. Shimoda, M.S. Schlissel, and G. Kelsoe. 1997. V(D)J recombinase activity in a subset of germinal center B lymphocytes. Science. 278:301-305.
48. Casellas, R., A. Nussenzweig, R. Wuerffel, R. Pelanda, A. Reichlin, H. Suh, X. Qin, E. Besmer, A. Kenter, K. Rajewsky, and M. Nussenzweig. 1998. Ku80 is required for immunoglobulin isotype switching. EMBO (Eur. Mol. Biol. Organ.) J. 17:2404-2411.
49. Hodgkin, P.D., J.H. Lee, and A.B. Lyons. 1996. B cell differentiation and isotype switching is related to division cycle number. J. Exp. Med. 184:277-281.
50. Zelazowski, P., E.E. Max, M.R. Kehry, and C.M. Snapper. 1997. Regulation of Ku expression in normal murine B cells by stimuli that promote switch recombination. J. Immunol. 159:2559-2562.
51. Blunt, T., N.J. Finnie, G.E. Taccioli, G.G. Smith, J. Demengeot, T.M. Gottlieb, R. Mizuta, A.J. Varghese, F.W. Alt, P.A. Jeggo, et al. 1995. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. Cell. 80:813-823.
52. Finnie, N.J., T.M. Gottlieb, T. Blunt, P.A. Jeggo, and S.P. Jackson. 1995. DNA-dependent protein kinase activity is absent in xrs-6 cells: implications for site-specific recombination and DNA double-strand break repair. Proc. Natl. Acad. Sci. USA. 92:320-324.
53. Taccioli, G.E., T.M. Gottlieb, T. Blunt, A. Priestley, J. Demengeot, R. Mizuta, A.R. Lehmann, F.W. Alt, S.P. Jackson, and P.A. Jeggo. 1994. Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Science. 265:1442-1445.
54. Smider, V., W.K. Rathmell, M.R. Lieber, and G. Chu. 1994. Restoration of X-ray resistance and V(D)J recombination in mutant cells by Ku cDNA. Science. 266:288-291.
55. Rathmell, W.K., and G. Chu. 1994. Involvement of the Ku autoantigen in the cellular response to DNA double-strand breaks. Proc. Natl. Acad. Sci. USA. 91:7623-7627.
56. Ramsden, D.A., and M. Gellert. 1998. Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double-strand breaks. EMBO (Eur. Mol. Biol. Organ.) J. 17:609-614.
57. Li, M.J., M.C. Peakman, E.I. Golub, G. Reddy, D.C. Ward, C.M. Radding, and N. Maizels. 1996. Rad51 expression and localization in B cells earning out class switch recombination. Proc. Natl. Acad. Sci. USA. 93:10222-10227.
58. Essers, J., R.W. Hendriks, S.M. Swagemakers, C. Troelstra, J. de Wit, D. Bootsma, J.H. Hoeijmakers, and R. Kanaar. 1997. Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination. Cell. 89: 195-204.
59. Boulton, S.J., and S.P. Jackson. 1996. Identification of a Saccharomyces cerevisiae Ku80 homologue: roles in DNA double strand break rejoining and in telomeric maintenance. Nucleic Acids Res. 24:4639-4648.
60. Boulton, S.J., and S.P. Jackson. 1996. Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways. EMBO (Eur. Mol. Biol. Organ.) J. 15:5093-5103.
61. Milne, G.T., S. Jin, K.B. Shannon, and D.T. Weaver. 1996. Mutations in two Ku homologs define a DNA end-joining repair pathway in Saccharomyces cerevisiae. Mol. Cell. Biol. 16: 4189-4198.
62. Siede, W., A.A. Friedl, I. Dianova, F. Eckardt-Schupp, and E.C. Friedberg. 1996. The Saccharomyces cerevisiae Ku autoantigen homologue affects radiosensitivity only in the absence of homologous recombination. Genetics. 142:91-102.
63. Liang, F., P.J. Romanienko, D.T. Weaver, P.A. Jeggo, and M. Jasin. 1996. Chromosomal double-strand break repair in Ku80-deficient cells. Proc. Natl. Acad. Sci. USA. 93:8929-8933.