Ongoing somatic hypermutation of the rearranged VH but not of the V-lambda gene in EBV-transformed rheumatoid factor-producing lymphoblastoid cell line

Molecular Immunology

Volumn 46, Issue 1, 2008, Pages 80-90

  Chezar, Ilan ^a   Lobel Lavi, Liat ^a   Steinitz, Michael ^b   Laskov, Reuven ^a  

^a HEBREW UNIVERSITY   (Israel)

^b HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

AID; Antibodies; B lymphocytes; Epstein Barr virus; Lymphoblastoid cell line; Rheumatoid factor; Somatic hypermutation

Indexed keywords

ACTIVATION INDUCED CYTIDINE DEAMINASE; CIS ACTING ELEMENT; IMMUNOGLOBULIN G; IMMUNOGLOBULIN G ANTIBODY; IMMUNOGLOBULIN HEAVY CHAIN; IMMUNOGLOBULIN LAMBDA CHAIN; RHEUMATOID FACTOR; TRANS ACTING FACTOR;

AMINO ACID SUBSTITUTION; ANTIBODY SPECIFICITY; ANTIGEN BINDING; ARTICLE; BINDING AFFINITY; CELL CLONE; CELL CULTURE; CELL DIVISION; CELL TRANSFORMATION; CONTROLLED STUDY; EPSTEIN BARR VIRUS; GENE REARRANGEMENT; GENE SEQUENCE; GENE TARGETING; GENETIC CODE; GERMINAL CENTER; HUMAN; HUMAN CELL; IMMUNOGLOBULIN VARIABLE REGION; LYMPHOBLASTOID CELL; POINT MUTATION; PRIORITY JOURNAL; PROTEIN MOTIF; SOMATIC HYPERMUTATION; SOMATIC MUTATION;

ADULT; AMINO ACID SEQUENCE; ANTIGENS; B-LYMPHOCYTES; BASE SEQUENCE; CELL TRANSFORMATION, VIRAL; DNA-BINDING PROTEINS; DNA-DIRECTED DNA POLYMERASE; GENE REARRANGEMENT, B-LYMPHOCYTE, HEAVY CHAIN; HERPESVIRUS 4, HUMAN; HUMANS; IMMUNOGLOBULIN HEAVY CHAINS; IMMUNOGLOBULIN LAMBDA-CHAINS; IMMUNOGLOBULIN VARIABLE REGION; MOLECULAR SEQUENCE DATA; MUTATION; MUTS HOMOLOG 2 PROTEIN; PHENOTYPE; RHEUMATOID FACTOR; SOMATIC HYPERMUTATION, IMMUNOGLOBULIN; URACIL-DNA GLYCOSIDASE;

HUMAN HERPESVIRUS 4;

EID: 52949111532     PISSN: 01615890     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.molimm.2008.07.002     Document Type: Article

References (61)

1. Adams C.L., Macleod M.K., James Milner-White E., Aitken R., Garside P., and Stott D.I. Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation. Immunology 108 (2003) 274-287
2. Albesiano E., Messmer B.T., Damle R.N., Allen S.L., Rai K.R., and Chiorazzi N. Activation-induced cytidine deaminase in chronic lymphocytic leukemia B cells: expression as multiple forms in a dynamic, variably sized fraction of the clone. Blood 102 (2003) 3333-3339
3. Allen C.D., Okada T., Tang H.L., and Cyster J.G. Imaging of germinal center selection events during affinity maturation. Science 315 (2007) 528-531
4. Bachl J., Carlson C., Gray-Schopfer V., Dessing M., and Olsson C. Increased transcription levels induce higher mutation rates in a hypermutating cell line. J. Immunol. 166 (2001) 5051-5057
5. Bachl J., and Wabl M. An immunoglobulin mutator that targets G.C base pairs. Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 851-855
6. Barreto V.M., Ramiro A.R., and Nussenzweig M.C. Activation-induced deaminase: controversies and open questions. Trends Immunol. 26 (2005) 90-96
7. Bhattacharya P., Grigera F., Rogozin I.B., McCarty T., Morse III H.C., and Kenter A.L. Identification of murine B cell lines that undergo somatic hypermutation focused to A:T and G:C residues. Eur. J. Immunol. 38 (2008) 227-239
8. Bransteitter R., Pham P., Scharff M.D., and Goodman M.F. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 4102-4107
9. Casali P., Pal Z., Xu Z., and Zan H. DNA repair in antibody somatic hypermutation. Trends Immunol. 27 (2006) 313-321
10. Corper A.L., Sohi M.K., Bonagura V.R., Steinitz M., Jefferis R., Feinstein A., Beale D., Taussig M.J., and Sutton B.J. Structure of human IgM rheumatoid factor Fab bound to its autoantigen IgG Fc reveals a novel topology of antibody-antigen interaction. Nat. Struct. Biol. 4 (1997) 374-381
11. Delbos F., Aoufouchi S., Faili A., Weill J.C., and Reynaud C.A. DNA polymerase eta is the sole contributor of A/T modifications during immunoglobulin gene hypermutation in the mouse. J. Exp. Med. 204 (2007) 17-23
12. Denepoux S., Fournier N., Peronne C., Banchereau J., and Lebecque S. T cells can induce somatic mutation in B cell receptor-engaged BL2 Burkitt's lymphoma cells independently of CD40-CD40 ligand interactions. J. Immunol. 164 (2000) 1306-1313
13. Diaz M., and Lawrence C. An update on the role of translesion synthesis DNA polymerases in Ig hypermutation. Trends Immunol. 26 (2005) 215-220
14. Diaz M., Verkoczy L.K., Flajnik M.F., and Klinman N.R. Decreased frequency of somatic hypermutation and impaired affinity maturation but intact germinal center formation in mice expressing antisense RNA to DNA polymerase zeta. J. Immunol. 167 (2001) 327-335
15. Dorner T., Brezinschek H.P., Brezinschek R.I., Foster S.J., Domiati-Saad R., and Lipsky P.E. Analysis of the frequency and pattern of somatic mutations within nonproductively rearranged human variable heavy chain genes. J. Immunol. 158 (1997) 2779-2789
16. Epeldegui M., Hung Y.P., McQuay A., Ambinder R.F., and Martinez-Maza O. Infection of human B cells with Epstein-Barr virus results in the expression of somatic hypermutation-inducing molecules and in the accrual of oncogene mutations. Mol. Immunol. 44 (2007) 934-942
17. Faili A., Aoufouchi S., Gueranger Q., Zober C., Leon A., Bertocci B., Weill J.C., and Reynaud C.A. AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell line. Nat. Immunol. 3 (2002) 815-821
18. Fukita Y., Jacobs H., and Rajewsky K. Somatic hypermutation in the heavy chain locus correlates with transcription. Immunity 9 (1998) 105-114
19. Gaidano G., Pasqualucci L., Capello D., Berra E., Deambrogi C., Rossi D., Maria Larocca L., Gloghini A., Carbone A., and Dalla-Favera R. Aberrant somatic hypermutation in multiple subtypes of AIDS-associated non-Hodgkin lymphoma. Blood 102 (2003) 1833-1841
20. Gil Y., Levy-Nabot S., Steinitz M., and Laskov R. Somatic mutations and activation-induced cytidine deaminase (AID) expression in established rheumatoid factor-producing lymphoblastoid cell line. Mol. Immunol. 44 (2007) 494-505
21. Gires O., Zimber-Strobl U., Gonnella R., Ueffing M., Marschall G., Zeidler R., Pich D., and Hammerschmidt W. Latent membrane protein 1 of Epstein-Barr virus mimics a constitutively active receptor molecule. EMBO J. 16 (1997) 6131-6140
22. Glasky M.S., and Reading C.L. Stability of specific immunoglobulin secretion by EBV-transformed lymphoblastoid cells and human-murine heterohybridomas. Hybridoma 8 (1989) 377-389
23. Gordon M.S., Kanegai C.M., Doerr J.R., and Wall R. Somatic hypermutation of the B cell receptor genes B29 (Igbeta, CD79b) and mb1 (Igalpha, CD79a). Proc. Natl. Acad. Sci. U.S.A. 100 (2003) 4126-4131
24. Goyenechea B., Klix N., Yelamos J., Williams G.T., Riddell A., Neuberger M.S., and Milstein C. Cells strongly expressing Ig(kappa) transgenes show clonal recruitment of hypermutation: a role for both MAR and the enhancers. EMBO J. 16 (1997) 3987-3994
25. Griffiths G.M., Berek C., Kaartinen M., and Milstein C. Somatic mutation and the maturation of immune response to 2-phenyl oxazolone. Nature 312 (1984) 271-275
26. He B., Raab-Traub N., Casali P., and Cerutti A. EBV-encoded latent membrane protein 1 cooperates with BAFF/BLyS and APRIL to induce T cell-independent Ig heavy chain class switching. J. Immunol. 171 (2003) 5215-5224
27. Jacob J., Kelsoe G., Rajewsky K., and Weiss U. Intraclonal generation of antibody mutants in germinal centres. Nature 354 (1991) 389-392
28. Klein U., Kuppers R., and Rajewsky K. Human IgM+IgD+ B cells, the major B cell subset in the peripheral blood, express V kappa genes with no or little somatic mutation throughout life. Eur. J. Immunol. 23 (1993) 3272-3277
29. Komori A., Xu Z., Wu X., Zan H., and Casali P. Biased dA/dT somatic hypermutation as regulated by the heavy chain intronic iEmu enhancer and 3'Ealpha enhancers in human lymphoblastoid B cells. Mol. Immunol. 43 (2006) 1817-1826
30. Lam K.P., Kuhn R., and Rajewsky K. In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 90 (1997) 1073-1083
31. Li Z., Woo C.J., Iglesias-Ussel M.D., Ronai D., and Scharff M.D. The generation of antibody diversity through somatic hypermutation and class switch recombination. Genes Dev. 18 (2004) 1-11
32. Liu M., Duke J.L., Richter D.J., Vinuesa C.G., Goodnow C.C., Kleinstein S.H., and Schatz D.G. Two levels of protection for the B cell genome during somatic hypermutation. Nature 451 (2008) 841-845
33. Longerich S., Basu U., Alt F., and Storb U. AID in somatic hypermutation and class switch recombination. Curr. Opin. Immunol. 18 (2006) 164-174
34. Martin A., and Scharff M.D. Somatic hypermutation of the AID transgene in B and non-B cells. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 12304-12308
35. Masuda K., Ouchida R., Takeuchi A., Saito T., Koseki H., Kawamura K., Tagawa M., Tokuhisa T., Azuma T., and O-Wang J. DNA polymerase theta contributes to the generation of C/G mutations during somatic hypermutation of Ig genes. Proc. Natl. Acad. Sci. U.S.A. 102 (2005) 13986-13991
36. Neuberger M.S., Di Noia J.M., Beale R.C., Williams G.T., Yang Z., and Rada C. Somatic hypermutation at A.T pairs: polymerase error versus dUTP incorporation. Nat. Rev. Immunol. 5 (2005) 171-178
37. Neuberger M.S., and Rada C. Somatic hypermutation: activation-induced deaminase for C/G followed by polymerase eta for A/T. J. Exp. Med. 204 (2007) 7-10
38. Oprea M., and Perelson A.S. Somatic mutation leads to efficient affinity maturation when centrocytes recycle back to centroblasts. J. Immunol. 158 (1997) 5155-5162
39. Oreskes I., and Mandel D. Reactivity of sized thermal aggregates of immunoglobulin G with IgM rheumatoid factor. Immunology 51 (1984) 115-121
40. Parsa J.Y., Basit W., Wang C.L., Gommerman J.L., Carlyle J.R., and Martin A. AID mutates a non-immunoglobulin transgene independent of chromosomal position. Mol. Immunol. 44 (2007) 567-575
41. Pasqualucci L., Migliazza A., Fracchiolla N., William C., Neri A., Baldini L., Chaganti R.S., Klein U., Kuppers R., Rajewsky K., and Dalla-Favera R. BCL-6 mutations in normal germinal center B cells: evidence of somatic hypermutation acting outside Ig loci. Proc. Natl. Acad. Sci. U.S.A. 95 (1998) 11816-11821
42. Pasqualucci L., Neumeister P., Goossens T., Nanjangud G., Chaganti R.S., Kuppers R., and Dalla-Favera R. Hypermutation of multiple proto-oncogenes in B-cell diffuse large-cell lymphomas. Nature 412 (2001) 341-346
43. Peng H.Z., Du M.Q., Koulis A., Aiello A., Dogan A., Pan L.X., and Isaacson P.G. Nonimmunoglobulin gene hypermutation in germinal center B cells. Blood 93 (1999) 2167-2172
44. Peters A., and Storb U. Somatic hypermutation of immunoglobulin genes is linked to transcription initiation. Immunity 4 (1996) 57-65
45. Rogozin I.B., and Diaz M. Cutting edge: DGYW/WRCH is a better predictor of mutability at G:C bases in Ig hypermutation than the widely accepted RGYW/WRCY motif and probably reflects a two-step activation-induced cytidine deaminase-triggered process. J. Immunol. 172 (2004) 3382-3384
46. Rogozin I.B., Pavlov Y.I., Bebenek K., Matsuda T., and Kunkel T.A. Somatic mutation hotspots correlate with DNA polymerase eta error spectrum. Nat. Immunol. 2 (2001) 530-536
47. Sale J.E., and Neuberger M.S. TdT-accessible breaks are scattered over the immunoglobulin V domain in a constitutively hypermutating B cell line. Immunity 9 (1998) 859-869
48. Schwickert T.A., Lindquist R.L., Shakhar G., Livshits G., Skokos D., Kosco-Vilbois M.H., Dustin M.L., and Nussenzweig M.C. In vivo imaging of germinal centres reveals a dynamic open structure. Nature 446 (2007) 83-87
49. Shen H.M., Michael N., Kim N., and Storb U. The TATA binding protein, c-Myc and survivin genes are not somatically hypermutated, while Ig and BCL6 genes are hypermutated in human memory B cells. Int. Immunol. 12 (2000) 1085-1093
50. Steinitz M., Klein G., Koskimies S., and Makel O. EB virus-induced B lymphocyte cell lines producing specific antibody. Nature 269 (1977) 420-422
51. Steinitz M., and Tamir S. Human monoclonal autoimmune antibody produced in vitro: rheumatoid factor generated by Epstein-Barr virus-transformed cell line. Eur. J. Immunol. 12 (1982) 126-133
52. Storb U., Shen H.M., Michael N., and Kim N. Somatic hypermutation of immunoglobulin and non-immunoglobulin genes. Philos. Trans. R. Soc. Lond. B Biol. Sci. 356 (2001) 13-19
53. Tumas-Brundage K., and Manser T. The transcriptional promoter regulates hypermutation of the antibody heavy chain locus. J. Exp. Med. 185 (1997) 239-250
54. Tumas-Brundage K., Vora K.A., Giusti A.M., and Manser T. Characterization of the cis-acting elements required for somatic hypermutation of murine antibody V genes using conventional transgenic and transgene homologous recombination approaches. Semin. Immunol. 8 (1996) 141-150
55. Wabl M., Burrows P.D., von Gabain A., and Steinberg C. Hypermutation at the immunoglobulin heavy chain locus in a pre-B-cell line. Proc. Natl. Acad. Sci. U.S.A. 82 (1985) 479-482
56. Wabl M., Jack H.M., Meyer J., Beck-Engeser G., von Borstel R.C., and Steinberg C.M. Measurements of mutation rates in B lymphocytes. Immunol. Rev. 96 (1987) 91-107
57. Wang C.L., Harper R.A., and Wabl M. Genome-wide somatic hypermutation. Proc. Natl. Acad. Sci. U.S.A. 101 (2004) 7352-7356
58. Xiao Z., Ray M., Jiang C., Clark A.B., Rogozin I.B., and Diaz M. Known components of the immunoglobulin A:T mutational machinery are intact in Burkitt lymphoma cell lines with G:C bias. Mol. Immunol. 44 (2007) 2659-2666
59. Yoshikawa K., Okazaki I.M., Eto T., Kinoshita K., Muramatsu M., Nagaoka H., and Honjo T. AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts. Science 296 (2002) 2033-2036
60. Zan H., Cerutti A., Dramitinos P., Schaffer A., Li Z., and Casali P. Induction of Ig somatic hypermutation and class switching in a human monoclonal IgM+ IgD+ B cell line in vitro: definition of the requirements and modalities of hypermutation. J. Immunol. 162 (1999) 3437-3447
61. Zan H., Shima N., Xu Z., Al-Qahtani A., Evinger Iii A.J., Zhong Y., Schimenti J.C., and Casali P. The translesion DNA polymerase theta plays a dominant role in immunoglobulin gene somatic hypermutation. EMBO J. 24 (2005) 3757-3769