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PMID: 1875929 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

High expression of a 3'----5' exonuclease activity is specific to B lymphocytes.

Molecular and cellular biology ·Vol. 11 ·No. 9 ·1991-09-00 ·Pages 4398-404

Kenter AL, Tredup J

Abstract

V(D)J joining, the immunoglobulin heavy-chain (IgH) class switch, and somatic hypermutation directed at variable regions are unique genetic recombination or mutation events which occur during B-cell differentiation. The enzymatic process directing and controlling these events remains obscure. An assay for exonucleolytic activity has been devised, and an exonuclease activity expressed at high levels in normal B lymphocytes has been detected. The high expression of this enzyme is specific to B lymphocytes and may be developmentally regulated. We have partially purified a B-cell-associated nuclease by column chromatography. Using this preparation, we have begun a rigorous analysis of its activity. This activity is a nonprocessive, 3'----5' exonuclease with a requirement for divalent cations. Our studies demonstrate that EDTA, poly(dI-dC), and glycerol are all inhibitory to B-cell-associated exonucleolytic activity. The exonuclease displays sequence preference but no sequence specificity when tested on a variety of native DNA substrates. This nuclease is distinct from other exonuclease activities previously described.

MeSH Terms
Animals B-Lymphocytes/enzymology Base Sequence Cells, Cultured DNA Exodeoxyribonuclease V Exodeoxyribonucleases/genetics,isolation & purification,metabolism Gene Expression Regulation, Enzymologic Mice Mice, Inbred BALB C Mice, Nude Molecular Sequence Data Organ Specificity/genetics Substrate Specificity
Chemicals
DNA Exodeoxyribonucleases Exodeoxyribonuclease V
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Kenter A L
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago 60680.
Tredup J
References (48)
48 references, click to expand
  1. The molecular evolution of the immune response: idiotope-specific suppression indicates that B cells express germ-line-encoded V genes prior to antigenic stimulation.
    Eur J Immunol. 1986 Nov;16(11):1439-44 PMID: 3490986
  2. Novikoff hepatoma deoxyribonucleic acid polymerase. Purification and properties of a homogeneous beta polymerase.
    Biochemistry. 1976 Jul 13;15(14):3114-21 PMID: 182203
  3. Cell cycle kinetics model of LPS-stimulated spleen cells correlates switch region rearrangements with S phase.
    J Immunol Methods. 1987 Feb 26;97(1):111-7 PMID: 3819434
  4. Colcemid inhibits growth during early G1 in normal but not in tumorigenic lymphocytes.
    Exp Cell Res. 1986 Nov;167(1):241-51 PMID: 3758204
  5. Molecular events during maturation of the immune response to oxazolone.
    Nature. 1985 Aug 1-7;316(6027):412-8 PMID: 3927173
  6. Detection of an immunoglobulin switch region-specific DNA-binding protein in mitogen-stimulated mouse splenic B cells.
    Mol Cell Biol. 1990 Apr;10(4):1714-8 PMID: 1690849
  7. Switch circular DNA formed in cytokine-treated mouse splenocytes: evidence for intramolecular DNA deletion in immunoglobulin class switching.
    Cell. 1990 Jul 13;62(1):135-42 PMID: 2114219
  8. Circular DNA is a product of the immunoglobulin class switch rearrangement.
    Nature. 1990 May 31;345(6274):452-6 PMID: 2111465
  9. Circular DNA is excised by immunoglobulin class switch recombination.
    Cell. 1990 Jul 13;62(1):143-9 PMID: 2364432
  10. Differentiated rat glial cell strain in tissue culture.
    Science. 1968 Jul 26;161(3839):370-1 PMID: 4873531
  11. Human correxonuclease. Purification and properties of a DNA repair exonuclease from placenta.
    J Biol Chem. 1976 Aug 10;251(15):4579-87 PMID: 947895
  12. Establishment of functional clonal lines of neurons from mouse neuroblastoma.
    Proc Natl Acad Sci U S A. 1969 Sep;64(1):311-5 PMID: 5263016
  13. Excision of pyrimidine dimers from ultraviolet-irradiated DNA by exonucleases from mammalian cells.
    Eur J Biochem. 1971 Feb 1;18(3):407-14 PMID: 5542950
  14. Origin of antibody variation.
    Nature. 1966 Jul 16;211(5046):242-3 PMID: 5965537
  15. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.
    Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 PMID: 6828386
  16. Excision repair and DNA synthesis with a combination of HeLa DNA polymerase beta and DNase V.
    J Biol Chem. 1983 Jan 10;258(1):108-18 PMID: 6848490
  17. Interaction of mammalian deoxyribonuclease V, a double strand 3' to 5' and 5' to 3' exonuclease, with deoxyribonucleic acid polymerase-beta from the Novikoff hepatoma.
    J Biol Chem. 1980 Nov 10;255(21):10239-47 PMID: 6253467
  18. Isotype switching in murine pre-B cell lines.
    Cell. 1983 Sep;34(2):545-56 PMID: 6311431
  19. Allelic inclusion in the pre-B-cell line 18-81.
    Proc Natl Acad Sci U S A. 1984 Feb;81(3):867-70 PMID: 6322175
  20. Double-stranded cleavage by cell extracts near recombinational signal sequences of immunoglobulin genes.
    Nature. 1984 Apr 26-May 2;308(5962):860-2 PMID: 6325923
  21. Isolation and characterization of endonuclease J: a sequence-specific endonuclease cleaving immunoglobulin genes.
    Nucleic Acids Res. 1984 Aug 10;12(15):5995-6010 PMID: 6089106
  22. Purification and characterization of DNase VII, a 3' leads to 5'-directed exonuclease from human placenta.
    J Biol Chem. 1981 Aug 10;256(15):8074-9 PMID: 6267037
  23. Clusters of point mutations are found exclusively around rearranged antibody variable genes.
    Proc Natl Acad Sci U S A. 1983 Jun;80(11):3439-43 PMID: 6222379
  24. Immunoglobulin class switching.
    Cell. 1984 Apr;36(4):801-3 PMID: 6608409
  25. Immunoglobulin heavy-chain constant-region genes.
    Cell. 1982 Jul;29(3):719-21 PMID: 6817925
  26. Switch from hapten-specific immunoglobulin M to immunoglobulin D secretion in a hybrid mouse cell line.
    Proc Natl Acad Sci U S A. 1981 Feb;78(2):1138-42 PMID: 6940132
  27. Somatic mutation gains its place among the generators of diversity.
    Cell. 1981 Nov;26(3 Pt 1):295-6 PMID: 7326743
  28. Immunoglobulin differentiation is dictated by repeated recombination sequences within the V region prototype gene: a hypothesis.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4598-602 PMID: 116234
  29. Site-specific DNA inversion is enhanced by a DNA sequence element in cis.
    Proc Natl Acad Sci U S A. 1985 Jun;82(11):3776-80 PMID: 16593573
  30. Antibody diversity: somatic hypermutation of rearranged VH genes.
    Cell. 1981 Dec;27(3 Pt 2):573-81 PMID: 6101208
  31. Molecular aspects of heavy-chain class switching.
    Crit Rev Immunol. 1989;9(3):173-200 PMID: 2505810
  32. DNA-repair reactions by purified HeLa DNA polymerases and exonucleases.
    J Biol Chem. 1988 Sep 5;263(25):12228-34 PMID: 2842325
  33. Exonucleolytic proofreading.
    Cell. 1988 Jun 17;53(6):837-40 PMID: 2838173
  34. Hypothesis: somatic hypermutation by gene conversion via the error prone DNA----RNA----DNA information loop.
    Mol Immunol. 1987 Jun;24(6):667-73 PMID: 2443841
  35. Endonucleolytic activity that cleaves immunoglobulin recombination sequences.
    Science. 1986 Mar 7;231(4742):1141-5 PMID: 3003919
  36. Hin-mediated site-specific recombination requires two 26 bp recombination sites and a 60 bp recombinational enhancer.
    Cell. 1985 Jul;41(3):781-91 PMID: 2988787
  37. Multiple DNA-protein interactions governing high-precision DNA transactions.
    Science. 1986 Sep 5;233(4768):1050-6 PMID: 2943018
  38. G inversion in bacteriophage Mu DNA is stimulated by a site within the invertase gene and a host factor.
    Cell. 1985 Jul;41(3):771-80 PMID: 3159478
  39. Immunoglobulin mRNA stability varies during B lymphocyte differentiation.
    EMBO J. 1988 Apr;7(4):1041-6 PMID: 3136013
  40. Appearance of cytolytic granules upon induction of cytolytic activity in CTL-hybrids.
    EMBO J. 1985 Oct;4(10):2533-8 PMID: 2414099
  41. Mapping cell surface antigens on mouse pre-B cell lines.
    Eur J Immunol. 1985 Mar;15(3):295-8 PMID: 2579825
  42. The role of somatic hypermutation in the generation of antibody diversity.
    Science. 1989 Jun 9;244(4909):1152-7 PMID: 2658060
  43. The V(D)J recombination activating gene, RAG-1.
    Cell. 1989 Dec 22;59(6):1035-48 PMID: 2598259
  44. V(D)J recombination: a functional definition of the joining signals.
    Genes Dev. 1989 Jul;3(7):1053-61 PMID: 2777075
  45. CH isotype 'switching' during normal B-lymphocyte development.
    Annu Rev Immunol. 1984;2:493-548 PMID: 6085751
  46. Processivity of DNA exonucleases.
    J Biol Chem. 1978 Jan 25;253(2):424-9 PMID: 338608
  47. Repair tracts in mismatched DNA heteroduplexes.
    Proc Natl Acad Sci U S A. 1976 Nov;73(11):4135-9 PMID: 1069303
  48. Developmental stage specificity of the lymphoid V(D)J recombination activity.
    Genes Dev. 1987 Oct;1(8):751-61 PMID: 3428598
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1991-09-00
Pages
4398-404
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC361302
Subset
IM
Grants
NIAID NIH HHS · R21 AI106328 · United States
NIGMS NIH HHS · GM39231 · United States
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