Class switching in B cells lacking 3' immunoglobulin heavy chain enhancers

Journal of Experimental Medicine

Volumn 188, Issue 8, 1998, Pages 1421-1431

  Manis, John P ^a,b   Van Der Stoep, Nienke ^a,b   Tian, Ming ^a,b   Ferrini, Roger ^a,b,c   Davidson, Laurie ^a,b   Bottaro, Andrea ^c   Alt, Frederick W ^a,b,c  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Class switching; Enhancers; Gene targeted mutation transcription; Immunoglobulin genes

Indexed keywords

BETA GLOBIN; IMMUNOGLOBULIN HEAVY CHAIN;

ANIMAL CELL; ARTICLE; B LYMPHOCYTE; CONTROLLED STUDY; EMBRYO; FLOW CYTOMETRY; GENE MUTATION; GENETIC RECOMBINATION; GENETIC TRANSCRIPTION; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SPLEEN CELL;

ANIMALS; B-LYMPHOCYTES; CELLS, CULTURED; ENHANCER ELEMENTS (GENETICS); GENES, REGULATOR; GLOBINS; IMMUNOGLOBULIN CLASS SWITCHING; IMMUNOGLOBULIN HEAVY CHAINS; IMMUNOGLOBULIN ISOTYPES; LIPOPOLYSACCHARIDES; MICE; MICE, INBRED C57BL; RECOMBINATION, GENETIC;

EID: 0032547798     PISSN: 00221007     EISSN: None     Source Type: Journal    
DOI: 10.1084/jem.188.8.1421     Document Type: Article

References (77)

1. Lansford, R., A. Okada, J. Chen, E. Oltz, T. Blackwell, F. Alt, and G. Rathburn. 1996. Mechanism and control of immunoglobulin gene rearrangement. In Molecular Immunology. Second edition. B. Hames and D. Glover, editors. Oxford University Press, Oxford. 248-282.
2. Zhang, J., F.W. Alt, and T. Honjo. 1995. Regulation of class switch recombination of the immunoglobulin heavy chain genes. In Immunoglobulin Genes. Second edition. T. Honjo and F.W. Alt, editors. Academic Press Limited, London. 235-265.
3. Snapper, C.M., and W.E. Paul. 1987. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 236:944-947.
4. Coffman, R.L., J. Ohara, M.W. Bond, J. Carty, A. Zlotnik, and W.E. Paul. 1986. B cell stimulatory factor-1 enhances the IgE response of lipopolysaccharide-activated B cells. J. Immunol. 136:4538-4541.
5. Kearney, J.F., M.D. Cooper, and A.R. Lawton. 1976. B lymphocyte differentiation induced by lipopolysaccharide. III. Suppression of B cell maturation by anti-mouse immunoglobulin antibodies. J. Immunol. 116:1664-1668.
6. Layton, J.E., E.S. Vitetta, J.W. Uhr, and P.H. Krammer. 1984. Clonal analysis of B cells induced to secrete IgG by T cell-derived lymphokine(s). J. Exp. Med. 160:1850-1863.
7. Yancopoulos, G.D., R.A. DePinho, K.A. Zimmerman, S.G. Lutzker, N. Rosenberg, and F.W. Alt. 1986. Secondary genomic rearrangement events in pre-B cells: VHDJH replacement by a LINE-1 sequence and directed class switching. EMBO (Eur. Mol. Biol. Organ.) J. 5:3259-3266.
8. Lutzker, S., P. Rothman, R. Pollock, R. Coffman, and F.W. Alt. 1988. Mitogen- and IL-4-regulated expression of germ-line Ig γ 2b transcripts: evidence for directed heavy chain class switching. Cell. 53:177-184.
9. Stavnezer, J., G. Radcliffe, Y.C. Lin, J. Nietupski, L. Berggren, R. Sitia, and E. Severinson. 1988. Immunoglobulin heavy-chain switching may be directed by prior induction of transcripts from constant-region genes. Proc. Natl. Acad. Sci. USA. 85:7704-7708.
10. Esser, C., and A. Radbruch. 1989. Rapid induction of transcription of unrearranged S gamma 1 switch regions in activated murine B cells by interleukin 4. EMBO (Eur. Mol. Biol. Organ.) J. 8:483-488.
11. Berton, M.T., J.W. Uhr, and E.S. Vitetta. 1989. Synthesis of germ-line gamma 1 immunoglobulin heavy-chain transcripts in resting B cells: induction by interleukin 4 and inhibition by interferon gamma. Proc. Natl. Acad. Sci. USA. 86:2829-2833.
12. Rothman, P., S. Lutzker, B. Gorham, V. Stewart, R. Coffman, and F. W. Alt. 1990. Structure and expression of germ-line immunoglobulin gamma 3 heavy chain gene transcripts: implications for mitogen and lymphokine directed class-switching. Int. Immunol. 2:621-627.
13. Rothman, P., Y.Y. Chen, S. Lutzker, S.C. Li, V. Stewart, R. Coffman, and F.W. Alt. 1990. Structure and expression of germ line immunoglobulin heavy-chain epsilon transcripts: interleukin-4 plus lipopolysaccharide-directed switching to C epsilon. Mol. Cell. Biol. 10:1672-1679.
14. Harriman, G.R., A. Bradley, S. Das, P. Rogers-Fani, and A.C. Davis. 1996. IgA class switch in I α exon-deficient mice. Role of germline transcription in class switch recombination. J. Clin. Invest. 97:477-485.
15. Xu, L., B. Gorham, S.C. Li, A. Bottaro, F.W. Alt, and P. Rothman. 1993. Replacement of germ-line epsilon promoter by gene targeting alters control of immunoglobulin heavy chain class switching. Proc. Natl. Acad. Sci. USA. 90:3705-3709.
16. Jung, S., K. Rajewsky, and A. Radbruch. 1993. Shutdown of class switch recombination by deletion of a switch region control element. Science. 259:984-987.
17. Zhang, J., A. Bottaro, S. Li, V. Stewart, and F.W. Alt. 1993. A selective defect in IgG2b switching as a result of targeted mutation of the I gamma 2b promoter and exon. EMBO (Eur. Mol. Biol. Organ.) J. 12:3529-3537.
18. 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.
19. Lorenz, M., S. Jung, and A. Radbruch. 1995. Switch transcripts in immunoglobulin class switching. Science. 267:1825-1828.
20. Coffman, R.L., D.A. Lebman, and P. Rothman. 1993. Mechanism and regulation of immunoglobulin isotype switching. Adv. Immunol. 54:229-270.
21. Bottaro, A., and F.W. Alt. 1997. Local and General Control Elements of Immunoglobulin Class Switch Recombination. IgE Regulation: Molecular Mechanisms. D. Vercelli, editor. John Wiley & Sons LTD, London. 155-177.
22. Gu, H., Y.R. Zou, and K. Rajewsky. 1993. Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting. Cell. 73:1155-1164.
23. Eckhardt, L.A., and B.K. Birshtem. 1985. Independent immunoglobulin class-switch events occurring in a single myelom cell line. Mol. Cell. Biol. 5:856-868.
24. Klein, S., T. Gerster, D. Picard, A. Radbruch, and W. Schaffner. 1985. Evidence for transient requirement of the IgH enhancer. Nucleic Acids Res. 13:8901-8912.
25. Wabl, M.R., and P.D. Burrows. 1984. Expression of immunoglobulin heavy chain at a high level in the absence of a proposed immunoglobulin enhancer element in cis. Proc. Natl. Acad. Sci. USA. 81:2452-2455.
26. Pettersson, S., G.P. Cook, M. Bruggemann, G.T. Williams, and M.S. Neuberger. 1990. A second B cell-specific enhancer 3′ of the immunoglobulin heavy-chain locus. Nature. 344:165-168.
27. Lieberson, R., S.L. Giannini, B.K. Birshtein, and L.A. Eckhardt. 1991. An enhancer at the 3′ end of the mouse immunoglobulin heavy chain locus. Nucleic Acids Res. 19:933-937.
28. Dariavach, P., G.T. Williams, K. Campbell, S. Pettersson, and M.S. Neuberger. 1991. The mouse IgH 3′-enhancer. Eur. J. Immunol. 21:1499-1504.
29. 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.
30. Lieberson, R., J. Ong, X. Shi, and L.A. Eckhardt. 1995. Immunoglobulin gene transcription ceases upon deletion of a distant enhancer. EMBO (Eur. Mol. Biol. Organ.) J. 14:6229-6238.
31. Matthias, P., and D. Baltimore. 1993. The immunoglobulin heavy chain locus contains another B-cell-specific 3′ enhancer close to the alpha constant region. Mol. Cell. Biol. 13: 1547-1553.
32. Madisen, L., and M. Groudine. 1994. Identification of a locus control region in the immunoglobulin heavy-chain locus that deregulates c-myc expression in plasmacytoma and Burkitt's lymphoma cells. Genes Dev. 8:2212-2226.
33. Michaelson, J.S., S.L. Giannini, and B.K. Birshtein, 1995. Identification of 3′ alpha-hs4, a novel Ig heavy chain enhancer element regulated at multiple stages of B cell differentiation. Nucleic Acids Res. 23:975-981.
34. Chauveau, C., and M. Cogne. 1996. Palindromic structure of the IgH 3′ locus control region [letter]. Nat. Genet. 14:15-16.
35. Saleque, S., M. Singh, R.D. Little, S.L. Giannini, J.S. Michaelson, and B.K. Birshtein. 1997. Dyad symmetry within the mouse 3′ IgH regulatory region includes two virtually identical enhancers (C alpha3′E and hs3). J. Immunol. 158:4780-4787.
36. Chen, C., and B.K. Birshtein. 1997. Virtually identical enhancers containing a segment of homology to murine 3′ IgH-E(hs1,2) lie downstream of human Ig C alpha 1 and C alpha 2 genes. J. Immunol. 159:1310-1318.
37. Mills, F.C., N. Harindranath, M. Mitchell, and E.E. Max. 1997. Enhancer complexes located downstream of both human immunoglobulin C α genes. J. Exp. Med. 186:845-858.
38. Martin, D.I., S. Fiering, and M. Groudine. 1996. Regulation of beta-globin gene expression: straightening out the locus. Curr. Opin. Genet. Dev. 6:488-495.
39. Kim, C.G., E.M. Epner, W.C. Forrester, and M. Groudine. 1992. Inactivation of the human beta-globin gene by targeted insertion into the beta-globin locus control region. Genes Dev. 6:928-938.
40. Fiering, S., E. Epner, K. Robinson, Y. Zhuang, A. Telling, M. Hu, D.I. Martin, T. Enver, T.J. Ley, and M. Groudine. 1995. Targeted deletion of 5′HS2 of the murine beta-globin LCR reveals that it is not essential for proper regulation of the beta-globin locus. Genes Dev. 9:2203-2213.
41. Hug, B.A., R.L. Wesselschmidt, S. Fiering, M.A. Bender, E. Epner, M. Groudine, and T.J. Ley. 1996. Analysis of mice containing a targeted deletion of beta-globin locus control region 5′ hypersensitive site 3. Mol. Cell Biol. 16:2906-2912.
42. Birshtein, B.K., C. Chen, S. Saleque, J.S. Michaelson, M. Singh, and R.D. Little. 1997. Murine and human 3′ IgH regulatory sequences. Curr. Top. Microbiol. Immunol. 224:73-80.
43. Gorman, J.R., N. van der Stoep, R. Monroe, M. Cogne, L. Davidson, and F.W. Alt. 1996. The Ig(kappa) enhancer influences the ratio of Ig(kappa) versus Ig(lambda) B lymphocytes. Immunity. 5:241-252.
44. 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.
45. Lakso, M., J.G. Pichel, J.R. Gorman, B. Sauer, Y. Okamoto, E. Lee, F.W. Alt, and H. Westphal. 1996. Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc. Natl. Acad. Sci. USA. 93:5860-5865.
46. Laird, P.W., A. Zijderveld, K. Linders, M.A. Rudnicki, R. Jaenisch, and A. Berns. 1991. Simplified mammalian DNA isolation procedure. Nucleic Acids Res. 19:4293.
47. 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.
48. Li, Y.S., K. Hayakawa, and R.R. Hardy. 1993. The regulated expression of B lineage associated genes during B cell differentiation in bone marrow and fetal liver. J. Exp. Med. 178:951-960.
49. Chen, J., R. Lansford, V. Stewart, F. Young, and F.W. Alt. 1993. RAG-2-deficient blastocyst complementation: an assay of gene function in lymphocyte development. Proc. Natl. Acad. Sci. USA. 90:4528-4532.
50. Arulampalam, V., C. Furebring, A. Samuelsson, U. Lendahl, C. Borrebaeck, I. Lundkvist, and S. Pettersson. 1996. Elevated expression levels of an Ig transgene in mice links the IgH 3′ enhancer to the regulation of IgH expression. Int. Immunol. 8:1149-1157.
51. Arulampalam, V., P.A. Grant, A. Samuelsson, U. Lendahl, and S. Pettersson. 1994. Lipopolysaccharide-dependent transactivation of the temporally regulated immunoglobulin heavy chain 3′ enhancer. Eur. J. Immunol. 24:1671-1677.
52. Grant, P.A., T. Andersson, M.F. Neurath, V. Arulampalam, A. Bauch, R. Muller, M. Reth, and S. Pettersson. 1996. A T cell controlled molecular pathway regulating the IgH locus: CD40-mediated activation of the IgH 3′ enhancer. EMBO (Eur. Mol. Biol. Organ.) J. 15:6691-6700.
53. Neurath, M.F., E.E. Max, and W. Strober. 1995. Pax5 (BSAP) regulates the murine immunoglobulin 3′ alpha enhancer by suppressing binding of NF-alpha P, a protein that controls heavy chain transcription. Proc. Natl. Acad. Sci. USA. 92:5336-5340.
54. Meyer, K.B., M. Skogberg, C. Margenfeld, J. Ireland, and S. Pettersson. 1995. Repression of the immunoglobulin heavy chain 3' enhancer by helix-loop-helix protein Id3 via a functionally important E47/E12 binding site: implications for developmental control of enhancer function. Eur. J. Immunol. 25:1770-1777.
55. Singh, M., and B.K. Birshtein. 1996. Concerted repression of an immunoglobulin heavy-chain enhancer, 3′ alpha E(hs1,2). Proc. Natl. Acad. Sci. USA. 93:4392-4397.
56. Tumas-Brundage, K.M., K.A. Vora, and T. Manser. 1997. Evaluation of the role of the 3′ alpha heavy chain enhancer [3′ alpha E(hs1,2)] in Vh gene somatic hypermutation. Mol. Immunol. 34:367-378.
57. Sha, W.C., H.C. Liou, E.I. Tuomanen, and D. Baltimore. 1995. Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses. Cell. 80: 321-330.
58. Michaelson, J.S., M. Singh, C.M. Snapper, W.C. Sha, D. Baltimore, and B.K. Birshtein. 1996. Regulation of 3′ IgH enhancers by a common set of factors, including kappa B-binding proteins. J. Immunol. 156:2828-2839.
59. Xu, Y., L. Davidson, F.W. Alt, and D. Baltimore. 1996. Deletion of the Ig kappa light chain intronic enhancer/matrix attachment region impairs but does not abolish V kappa J kappa rearrangement. Immunity. 4:377-385.
60. Baron, M.H. 1997. Transcriptional control of globin gene switching during vertebrate development. Biochim. Biophys. Acta. 1351:51-72.
61. Blom van Assendelft, G., O. Hanscombe, F. Grosveld, and D.R. Greaves. 1989. The beta-globin dominant control region activates homologous and heterologous promoters in a tissue-specific manner. Cell. 56:969-977.
62. Grosveld, F., G.B. van Assendelft, D.R. Greaves, and G. Kollias. 1987. Position-independent, high-level expression of the human beta-globin gene in transgenic mice. Cell. 51: 975-985.
63. Behringer, R.R., T.M. Ryan, R.D. Palmiter, R.L. Brinster, and T.M. Townes. 1990. Human gamma- to beta-globin gene switching in transgenic mice. Genes Dev. 4:380-389.
64. Forrester, W.C., E. Epner, M.C. Driscoll, T. Enver, M. Brice, T. Papayannopoulou, and M. Groudine. 1990. A deletion of the human beta-globin locus activation region causes a major alteration in chromatin structure and replication across the entire beta-globin locus. Genes Dev. 4:1637-1649.
65. Driscoll, M.C., C.S. Dobkin, and B.P. Alter. 1989. Gamma delta beta-thalassemia due to a de novo mutation deleting the 5′ beta-globin gene activation-region hypersensitive sites. Proc. Natl. Acad. Sci. USA. 86:7470-7474.
66. Gregor, P.D., and S.L. Morrison. 1986. Myeloma mutant with a novel 3′ flanking region: loss of normal sequence and insertion of repetitive elements leads to decreased transcription but normal processing of the alpha heavy-chain gene products. Mol. Cell. Biol. 6:1903-1916.
67. Chen, J., F. Young, A. Bottaro, V. Stewart, R.K. Smith, and F.W. Alt. 1993. Mutations of the intronic IgH enhancer and its flanking sequences differentially affect accessibility of the JH locus. EMBO (Eur. Mol. Biol. Organ.) J. 12:4635-4645.
68. Serwe, M., and F. Sablitzky. 1993. V(D)J recombination in B cells is impaired but not blocked by targeted deletion of the immunoglobulin heavy chain intron enhancer. HMBO (Eur. Mol. Biol. Organ.) J. 12:2321-2327.
69. Olson, E.N., H.H. Arnold, P.W. Rigby, and B.J. Wold. 1996. Know your neighbors: three phenotypes in null mutants of the myogenic bHLH gene MRF4. Cell. 85:1-4.
70. Pham, C.T., D.M. MacIvor, B.A. Hug, J.W. Heusel, and T.J. Ley. 1996. Long-range disruption of gene expression by a selectable marker cassette. Proc. Natl. Acad. Sci. USA. 93: 13090-13095.
71. Hanscombe, O., D. Whyatt, P. Fraser, N. Yannoutsos, D. Greaves, N. Dillon, and F. Grosveld. 1991. Importance of globin gene order for correct developmental expression. Genes Dev. 5:1387-1394.
72. Wijgerde, M., F. Grosveld, and P. Fraser. 1995. Transcription complex stability and chromatin dynamics in vivo. Nature. 377:209-213.
73. Walters, M.C., S. Fiering, J. Eidemiller, W. Magis, M. Groudine, and D.I. Martin. 1995. Enhancers increase the probability but not the level of gene expression. Proc. Natl. Acad. Sci. USA. 92:7125-7129.
74. Dillon, N., T. Trimborn, J. Strouboulis, P. Fraser, and F. Grosveld. 1998. The effect of distance on long-range chromatin interactions. Mol. Cell. 1:131-139.
75. Walters, M.C., W. Magis, S. Fiering, J. Eidemiller, D. Scalzo, M. Groudine, and D.I. Martin. 1996. Transcriptional enhancers act in cis to suppress position-effect variegation. Genes Dev. 10:185-195.
76. Bottaro, A., F. Young, J. Chen, M. Serwe, F. Sablitzky, and F. Alt. 1998. Deletion of the IgH intronic enhancer and associated matrix-attachment regions decreases, but does not abolish class switching at the μ locus. Int. Immunol. 10:799-806.
77. Enver, T., N. Raich, A.J. Ebens, T. Papayannopoulou, F. Costantini, and G. Stamatoyannopoulos. 1990. Developmental regulation of human fetal-to-adult globin gene switching in transgenic mice. Nature. 344:309-313.