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PMID: 6420495 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Multiple VH gene segments encode murine antistreptococcal antibodies.

The Journal of experimental medicine ·Vol. 159 ·No. 1 ·1984-01-01 ·Pages 179-92

Perlmutter RM, Klotz JL, Bond MW, Nahm M, Davie JM, Hood L

Abstract

Most mouse strains are able to mount a diverse antibody response against group A streptococcal carbohydrate (GAC). We have previously reported that murine anti-GAC antibodies are for the most part restricted to IgM and IgG3 subclasses. In addition, despite extensive heterogeneity in their isoelectric focusing patterns, greater than 50% of A/J anti-GAC antibodies share a common light chain defined by spectrotypic and idiotypic (VK1GAC) criteria. We have used protein and DNA sequencing strategies to examine the genetic basis of diversity in murine anti-GAC antibodies. In particular, we report that, (a) multiple, closely homologous VH gene segments contribute to the generation of anti-GAC antibodies, (b) a common framework sequence, related to the VK27 subgroup, probably defines VK1GAC, and (c) the A/J anti-GAC VH regions and BALB/c anti-inulin VH sequences are 95% homologous at the protein level and are likely encoded by overlapping VH gene families. Lastly, we discuss the genetic mechanisms that might permit the evolution of multiple, closely homologous germline VH gene segments in the context of highly divergent flanking region sequences.

MeSH Terms
Alleles Animals Antibodies, Bacterial/biosynthesis,genetics Antibody Diversity Cloning, Molecular Genetic Code Hybridomas/immunology Immunoglobulin Heavy Chains/genetics,immunology Immunoglobulin Variable Region/genetics,immunology Inulin/immunology Mice Mice, Inbred A Mice, Inbred BALB C Mice, Inbred C57BL Phosphorylcholine/immunology Polysaccharides, Bacterial/genetics,immunology
Chemicals
Antibodies, Bacterial Immunoglobulin Heavy Chains Immunoglobulin Variable Region Polysaccharides, Bacterial streptococcal polysaccharide group A Phosphorylcholine Inulin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Perlmutter R M
Klotz J L
Bond M W
Nahm M
Davie J M
Hood L
References (43)
43 references, click to expand
  1. T and B cells that recognize the same antigen do not transcribe similar heavy chain variable region gene segments.
    J Exp Med. 1983 Jul 1;158(1):192-209 PMID: 6190977
  2. 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
  3. Analysis of antibody diversity: V-D-J mRNA nucleotide sequence of four anti-GAT monoclonal antibodies. A paucigene system using alternate D-J recombinations to generate functionally similar hypervariable regions.
    EMBO J. 1983;2(6):867-72 PMID: 6416834
  4. Immunoglobulin genes.
    Annu Rev Immunol. 1983;1:499-528 PMID: 6443559
  5. Antibody diversity: somatic hypermutation of rearranged VH genes.
    Cell. 1981 Dec;27(3 Pt 2):573-81 PMID: 6101208
  6. A membrane-filter technique for the detection of complementary DNA.
    Biochem Biophys Res Commun. 1966 Jun 13;23(5):641-6 PMID: 5963888
  7. Idiotype expression and the inheritance of mouse antibody clones.
    J Exp Med. 1973 Mar 1;137(3):603-21 PMID: 4120285
  8. Mouse strain-specific idiotypy and interstrain idiotypic cross-reactions.
    J Immunol. 1974 Aug;113(2):522-30 PMID: 4858626
  9. Immunochemical and chemical studies on streptococcal group-specific carbohydrates.
    J Immunol. 1975 Jun;114(6):1654-8 PMID: 165237
  10. The organization, expression, and evolution of antibody genes and other multigene families.
    Annu Rev Genet. 1975;9:305-53 PMID: 813561
  11. Structural studies on induced antibodies with defined idiotypic specificities. III. N-terminal amino acid sequence of the heavy and light chains of mouse anti-streptococcal antibodies--A5A, S8, and S117.
    J Immunol. 1976 Jul;117(1):7-10 PMID: 819584
  12. A general method for isolation of high molecular weight DNA from eukaryotes.
    Nucleic Acids Res. 1976 Sep;3(9):2303-8 PMID: 987581
  13. Rapid analysis of amino acid phenylthiohydantoins by high-performance liquid chromatography.
    Anal Biochem. 1977 Feb;77(2):569-73 PMID: 842843
  14. Complete sharing of light chain spectrotypes by murine IgM and IgG anti-streptococcal antibodies.
    J Immunol. 1977 Jun;118(6):2161-6 PMID: 405425
  15. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I.
    J Mol Biol. 1977 Jun 15;113(1):237-51 PMID: 881736
  16. Packaging recombinant DNA molecules into bacteriophage particles in vitro.
    Proc Natl Acad Sci U S A. 1977 Aug;74(8):3259-63 PMID: 333431
  17. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  18. Sequence variation among heavy chains from inulin-binding myeloma proteins.
    Proc Natl Acad Sci U S A. 1978 Apr;75(4):1957-61 PMID: 417344
  19. Direct microsequence analysis of polypeptides using an improved sequenator, a nonprotein carrier (polybrene), and high pressure liquid chromatography.
    Biochemistry. 1978 May 30;17(11):2124-33 PMID: 667015
  20. Light chain diversity of murine anti-streptococcal antibodies: IgCH-linked effects on L chain expression.
    J Immunol. 1978 Jul;121(1):149-58 PMID: 97345
  21. Subclass restriction of murine anti-carbohydrate antibodies.
    J Immunol. 1978 Aug;121(2):566-72 PMID: 79606
  22. The isolation of structural genes from libraries of eucaryotic DNA.
    Cell. 1978 Oct;15(2):687-701 PMID: 719759
  23. New protein sequenator with increased sensitivity.
    Science. 1980 Feb 1;207(4430):523-5 PMID: 7352258
  24. 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
  25. A short primer for sequencing DNA cloned in the single-stranded phage vector M13mp2.
    Nucleic Acids Res. 1980 Apr 25;8(8):1731-43 PMID: 6253946
  26. A bacteriophage lambda vector for cloning large DNA fragments made with several restriction enzymes.
    Gene. 1980 Aug;10(3):249-59 PMID: 6254843
  27. Sequence organization of feline leukemia virus DNA in infected cells.
    Nucleic Acids Res. 1980 Aug 11;8(15):3287-305 PMID: 6255412
  28. The bidirectional transfer of DNA and RNA to nitrocellulose or diazobenzyloxymethyl-paper.
    Anal Biochem. 1980 Nov 15;109(1):123-9 PMID: 6162401
  29. IgG antibodies to phosphorylcholine exhibit more diversity than their IgM counterparts.
    Nature. 1981 May 7;291(5810):29-34 PMID: 7231520
  30. Gene conversion: some implications for immunoglobulin genes.
    Cell. 1981 Jun;24(3):592-4 PMID: 7018693
  31. Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a gamma 2a variable region.
    Cell. 1981 Jun;24(3):625-37 PMID: 6788376
  32. A simple method for estimating the probable numbers of different antibodies by examining the repeat frequencies of sequences or isoelectric focusing patterns.
    Mol Immunol. 1981 Jan;18(1):29-38 PMID: 6790935
  33. Somatic mutation of immunoglobulin light-chain variable-region genes.
    Cell. 1981 Jul;25(1):47-58 PMID: 6791832
  34. 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
  35. Organization, structure, and assembly of immunoglobulin heavy chain diversity DNA segments.
    J Exp Med. 1982 Jan 1;155(1):201-18 PMID: 6798155
  36. Somatic diversification is required to generate the V kappa genes of MOPC 511 and MOPC 167 myeloma proteins.
    Proc Natl Acad Sci U S A. 1981 Dec;78(12):7674-8 PMID: 6801657
  37. Monoclonal antibodies to streptococcal group A carbohydrate. I. A dominant idiotypic determinant is located on Vk.
    J Immunol. 1982 Oct;129(4):1513-8 PMID: 6180013
  38. Murine VK25 isotype sequence: monoclonal antibody 2S1.3 specific for the group A streptococcal polysaccharide.
    Hoppe Seylers Z Physiol Chem. 1982 Sep;363(9):1069-76 PMID: 7141411
  39. Genetic control of immunoglobulin production.
    Hosp Pract (Off Ed). 1983 Feb;18(2):73-82 PMID: 6401683
  40. Classification of mouse VK groups based on the partial amino acid sequence to the first invariant tryptophan: impact of 14 new sequences from IgG myeloma proteins.
    Mol Immunol. 1982 Dec;19(12):1619-30 PMID: 7162519
  41. The genetic basis of antibody production: a single heavy chain variable region gene encodes all molecules bearing the dominant anti-arsonate idiotype in the strain A mouse.
    Eur J Immunol. 1983 Feb;13(2):123-32 PMID: 6403356
  42. Somatic generation of antibody diversity.
    Nature. 1983 Apr 14;302(5909):575-81 PMID: 6300689
  43. mRNA sequences define an unusually restricted IgG response to 2-phenyloxazolone and its early diversification.
    Nature. 1983 Jul 28-Aug 3;304(5924):320-4 PMID: 6877353
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1984-01-01
Pages
179-92
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2187198
Subset
IM
Grants
NIAID NIH HHS · AI15353 · United States
NIAID NIH HHS · AI15926 · United States
NIAID NIH HHS · AI18088 · United States
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