Home LiteratureArticle Details
PMID: 3127529 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Point mutations cause the somatic diversification of IgM and IgG2a antiphosphorylcholine antibodies.

The Journal of experimental medicine ·Vol. 167 ·No. 3 ·1988-03-01 ·Pages 954-73

Chien NC, Pollock RR, Desaymard C, Scharff MD

Abstract

The genetic mechanism responsible for the somatic diversification of two mAbs was determined. The two PC-binding hybridomas were representative of events early and late in the immune response. The P28 cell line that produces an IgM antibody and thus represents events early in the immune response, was found to have 3 bp changes in its heavy chain variable (VH) region, with some changes in antibody affinity or specificity. The RP93 cell line that produces an IgG2a antibody and thus represents later events in the immune response, was found to have 9 bp changes in its VH region resulting in decreased affinity for PC and altered specificity. Oligonucleotides specific for linked base changes in the second hypervariable regions of both of these antibodies were used to look for previously undescribed V regions or other donor sequences that could have been responsible for these base changes. Since no donor sequences were found, we have concluded that somatic point mutation rather than gene conversion, V region replacement or the expression of an unidentified germline VH region gene is truly responsible for at least some of the somatic diversification of these antibodies.

MeSH Terms
Amino Acid Sequence Animals Antibodies, Monoclonal/genetics,immunology Antibody Diversity Base Sequence Binding Sites, Antibody Choline/analogs & derivatives Genes, Immunoglobulin Immunoglobulin G/genetics,immunology Immunoglobulin Heavy Chains/genetics Immunoglobulin M/genetics,immunology Immunoglobulin Variable Region/genetics Mice Mice, Inbred BALB C/genetics,immunology Molecular Sequence Data Mutation Phosphorylcholine/immunology
Chemicals
Antibodies, Monoclonal Immunoglobulin G Immunoglobulin Heavy Chains Immunoglobulin M Immunoglobulin Variable Region Phosphorylcholine Choline
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chien N C
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461.
Pollock R R
Desaymard C
Scharff M D
References (57)
57 references, click to expand
  1. Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma.
    Nature. 1986 Aug 28-Sep 3;322(6082):843-6 PMID: 3092106
  2. A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production.
    Nature. 1986 Aug 28-Sep 3;322(6082):840-2 PMID: 3092105
  3. Paucity of phosphorylcholine-specific clones in B cells expressing the VHT15 gene product.
    J Exp Med. 1986 Dec 1;164(6):2107-12 PMID: 3491177
  4. A hyperconversion mechanism generates the chicken light chain preimmune repertoire.
    Cell. 1987 Feb 13;48(3):379-88 PMID: 3100050
  5. Highly preferential VH-VL pairing in normal B cells results in antigen-independent selection of the available repertoire.
    J Immunol. 1987 Mar 1;138(5):1607-12 PMID: 3100643
  6. Evolution of antibody variable region structure during the immune response.
    Immunol Rev. 1987 Apr;96:141-62 PMID: 3298006
  7. Mutation drift and repertoire shift in the maturation of the immune response.
    Immunol Rev. 1987 Apr;96:23-41 PMID: 3298007
  8. Somatic mutation in anti-phosphorylcholine antibodies.
    Immunol Rev. 1987 Apr;96:59-74 PMID: 3298010
  9. Variability in the lambda light chain sequences of mouse antibody.
    Nature. 1970 Dec 12;228(5276):1045-7 PMID: 5483159
  10. Affinity labeling of a phosphorylcholine binding mouse myeloma protein.
    Biochemistry. 1972 Feb 29;11(5):766-71 PMID: 5059886
  11. Growth of primary plasmacytomas in the mineral oil-conditioned peritoneal environment.
    J Natl Cancer Inst. 1972 Jul;49(1):305-8 PMID: 5037438
  12. Clonal nature of the immune response to phosphorylcholine. IV. Idiotypic uniformity of binding site-associated antigenic determinants among mouse antiphosphorylcholine antibodies.
    J Exp Med. 1974 Sep 1;140(3):673-86 PMID: 4137581
  13. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  14. A sedimentation equilibrium method for determining molecular weights of proteins with a tabletop high speed air turbine centrifuge.
    J Biol Chem. 1978 Apr 10;253(7):2073-7 PMID: 632258
  15. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  16. Phosphorylcholine-binding hybridoma proteins of normal and idiotypically suppressed BALB/c mice I. Characterization and idiotypic analysis.
    Eur J Immunol. 1980 Apr;10(4):258-63 PMID: 6967409
  17. Phosphorylcholine-binding hybridoma proteins of normal and idiotypically suppressed BALB/c mice II. Variable region N-terminal amino acid sequences.
    Eur J Immunol. 1980 Apr;10(4):264-7 PMID: 6772452
  18. J genes for heavy chain immunoglobulins of mouse.
    Science. 1980 Sep 5;209(4461):1128-32 PMID: 6250219
  19. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes.
    Nature. 1980 Aug 14;286(5774):676-83 PMID: 6774258
  20. Cloned human and mouse kappa immunoglobulin constant and J region genes conserve homology in functional segments.
    Cell. 1980 Nov;22(1 Pt 1):197-207 PMID: 6775818
  21. The sequence at the 3' terminus of mouse immunoglobulin secreted mu chain messenger RNA determined from cloned cDNA.
    Nucleic Acids Res. 1980 Feb 25;8(4):703-13 PMID: 6776490
  22. Complete nucleotide sequence of mouse immunoglobulin mu gene and comparison with other immunoglobulin heavy chain genes.
    Nucleic Acids Res. 1980 Sep 11;8(17):3933-45 PMID: 6255422
  23. Ligand-affinity sedimentation equilibrium using an air-driven ultracentrifuge.
    Arch Biochem Biophys. 1980 Jul;202(2):507-14 PMID: 7458332
  24. The nucleotide sequence of a 5.5-kilobase DNA segment containing the mouse kappa immunoglobulin J and C region genes.
    J Biol Chem. 1981 May 25;256(10):5116-20 PMID: 6262318
  25. The complete nucleotide sequence of mouse immunoglobin gamma 2a gene and evolution of heavy chain genes: further evidence for intervening sequence-mediated domain transfer.
    Nucleic Acids Res. 1981 Mar 25;9(6):1365-81 PMID: 6262729
  26. Somatic mutation of immunoglobulin light-chain variable-region genes.
    Cell. 1981 Jul;25(1):47-58 PMID: 6791832
  27. A single VH gene segment encodes the immune response to phosphorylcholine: somatic mutation is correlated with the class of the antibody.
    Cell. 1981 Jul;25(1):59-66 PMID: 6791833
  28. Somatically generated mouse myeloma variants synthesizing IgA half-molecules.
    J Exp Med. 1981 Nov 1;154(5):1554-69 PMID: 7299348
  29. Immune response to phosphorylcholine. IX. Characterization of hybridoma anti-TEPC15 antibodies.
    J Immunol. 1982 Feb;128(2):595-9 PMID: 7033381
  30. Two kappa immunoglobulin genes are expressed in the myeloma S107.
    Cell. 1981 Oct;26(1 Pt 1):57-66 PMID: 6799208
  31. Antibody diversity: somatic hypermutation of rearranged VH genes.
    Cell. 1981 Dec;27(3 Pt 2):573-81 PMID: 6101208
  32. One heavy chain variable region gene segment subfamily in the BALB/c mouse contains 500-1000 or more members.
    Cell. 1986 Nov 7;47(3):461-70 PMID: 3094964
  33. The immune response of BALB/c mice to phosphorylcholine is restricted to a limited number of VH- and VL-isotypes.
    Mol Immunol. 1981 Dec;18(12):1027-33 PMID: 6801477
  34. Single amino acid substitution altering antigen-binding specificity.
    Proc Natl Acad Sci U S A. 1982 Mar;79(6):1979-83 PMID: 6804947
  35. Restriction in IgM expression. IV. Affinity analysis of monoclonal anti-phosphorylcholine antibodies.
    J Immunol. 1983 Jan;130(1):313-6 PMID: 6847884
  36. The equilibrium constant for the interaction between a monoclonal Fab fragment and an influenza virus neuraminidase.
    J Immunol. 1983 Mar;130(3):1313-6 PMID: 6822736
  37. Somatic generation of antibody diversity.
    Nature. 1983 Apr 14;302(5909):575-81 PMID: 6300689
  38. 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
  39. Recombination between antibody heavy chain variable-region genes: evidence for gene conversion.
    Proc Natl Acad Sci U S A. 1983 Aug;80(16):4997-5001 PMID: 6308665
  40. Immunoglobulin heavy chain class switch from IgM to IgG in a hybridoma.
    Eur J Immunol. 1983 Aug;13(8):614-9 PMID: 6884421
  41. Amino acid sequence of a phosphocholine-binding antibody from an immune defective CBA/N mouse employing the T15 VH region associated with unusual DH, JH, and V kappa segments.
    J Immunol. 1984 Mar;132(3):1544-9 PMID: 6420465
  42. Immunologic memory to phosphocholine. IV. Hybridomas representative of Group I (T15-like) and Group II (non-T15-like) antibodies utilize distinct VH genes.
    J Immunol. 1984 Mar;132(3):1550-5 PMID: 6420466
  43. Immunologic memory to phosphocholine. V. Hybridomas representative of group II antibodies utilize V kappa 1-3 gene(s).
    J Immunol. 1984 Mar;132(3):1556-60 PMID: 6420467
  44. Ordered rearrangement of immunoglobulin heavy chain variable region segments.
    EMBO J. 1984 Jun;3(6):1209-19 PMID: 6086308
  45. The generation of diversity in phosphorylcholine-binding antibodies.
    Adv Immunol. 1984;35:1-37 PMID: 6431763
  46. Somatic mutation of the T15 heavy chain gives rise to an antibody with autoantibody specificity.
    Proc Natl Acad Sci U S A. 1984 Sep;81(18):5841-4 PMID: 6435121
  47. The identification of monoclonal class switch variants by sib selection and an ELISA assay.
    J Immunol Methods. 1984 Nov 30;74(2):307-15 PMID: 6438240
  48. Rat anti-T15 monoclonal antibodies with specificity for VH- and VH-VL epitopes.
    Mol Immunol. 1984 Oct;21(10):961-7 PMID: 6209566
  49. Somatic mutation and the maturation of immune response to 2-phenyl oxazolone.
    Nature. 1984 Nov 15-21;312(5991):271-5 PMID: 6504141
  50. VH genes encoding the immune response to beta-(1,6)-galactan: somatic mutation in IgM molecules.
    EMBO J. 1984 Dec 1;3(12):3023-30 PMID: 6098462
  51. Inter- and intraclonal diversity in the antibody response to influenza hemagglutinin.
    J Exp Med. 1985 Apr 1;161(4):687-704 PMID: 3920342
  52. Mitotic recombination in germ cells generated two major histocompatibility complex mutant genes shown to be identical by RNA sequence analysis: Kbm9 and Kbm6.
    Proc Natl Acad Sci U S A. 1986 May;83(10):3371-5 PMID: 3458188
  53. Analysis of somatic cell H-2 variants to define the structural requirements for class I antigen expression.
    J Immunol. 1986 Aug 1;137(3):897-903 PMID: 3722821
  54. Lack of expression of the VHS107 gene family in the lipopolysaccharide-sensitive B cell subset of X-linked immunodeficiency-defective mice.
    J Exp Med. 1986 Jul 1;164(1):357-62 PMID: 3088200
  55. Sequence homology requirements for intermolecular recombination in mammalian cells.
    Proc Natl Acad Sci U S A. 1986 Jul;83(14):5199-203 PMID: 3523485
  56. Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution.
    Science. 1986 Aug 15;233(4765):747-53 PMID: 2426778
  57. Antibody diversity. New mechanism revealed.
    Nature. 1986 Aug 28-Sep 3;322(6082):772-3 PMID: 3092104
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.167.3.954
Published
1988-03-01
Pages
954-73
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2188873
Subset
IM
Grants
NIAID NIH HHS · AI-05231 · United States
NIAID NIH HHS · AI-10702 · United States
NCI NIH HHS · CA-39838 · United States
Databases
GENBANK
Y00650
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1084/jem.167.3.954 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2