Abstract
The germ-line elements for the variable (V) and joining (J) regions of the kappa chains (V kappa-Ars, J kappa 1) that give rise to the productive allele for the A/J mouse light chains of Ars-A monoclonal antibodies (directed against the hapten p-azophenylarsonate) have been cloned and sequenced as well as a rearranged Ars-A light chain gene. Using the V kappa-Ars gene as a hybridization probe, we provide evidence that the V kappa 10 family is relatively small and that only one member gives rise to the productive allele in all Ars-A antibodies. An unusual feature of Ars-A light chains is that all contain an arginine at position 96, the V-J junctional position. We had shown by chain recombination that arginine-96 was essential for antigen binding. In the present study, an arginine codon was not found either at the 3' end of the V kappa-Ars gene segment or at the 5' end of J kappa 1. However, an arginine codon (CGG) can easily be generated by recombination between these two germ-line elements. Thus, we document that junctional diversity through intracodonic recombination can be crucial to the antibody binding function of the resulting molecule.
MeSH Terms
Alleles
Animals
Antibodies, Monoclonal/genetics
Arginine/genetics
Cloning, Molecular
DNA
Genes
Hybridomas/physiology
Immunoglobulin Variable Region
Immunoglobulin kappa-Chains/genetics
Mice
Mice, Inbred Strains
Nucleic Acid Hybridization
Recombination, Genetic
Chemicals
Antibodies, Monoclonal
Immunoglobulin Variable Region
Immunoglobulin kappa-Chains
DNA
Arginine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sanz I
Capra J D
References (23)
23 references, click to expand
-
DNA sequencing with chain-terminating inhibitors.
Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7
PMID: 271968
-
Germ-line sequence of the DH segment employed in Ars-A antibodies: implications for the generation of junctional diversity.
J Immunol. 1986 Jul 1;137(1):362-5
PMID: 3011910
-
IgG antibodies to phosphorylcholine exhibit more diversity than their IgM counterparts.
Nature. 1981 May 7;291(5810):29-34
PMID: 7231520
-
Molecular cloning of an immunoglobulin kappa constant gene from NZB mouse.
Gene. 1981 Mar;13(2):163-172
PMID: 6453743
-
Conversations with Niels Kaj Jerne on immune regulation: associative versus network recognition.
Cell Immunol. 1981 Jul 1;61(2):425-36
PMID: 6166399
-
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
-
Complete amino acid sequence of light chain variable regions derived from five monoclonal anti-p-azophenylarsonate antibodies differing with respect to a crossreactive idiotype.
Proc Natl Acad Sci U S A. 1981 Dec;78(12):7679-83
PMID: 6801658
-
Somatic mutation in genes for the variable portion of the immunoglobulin heavy chain.
Science. 1982 Apr 16;216(4543):309-11
PMID: 6801765
-
VH families in the antibody response to p-azophenylarsonate: correlation between serology and amino acid sequence.
J Immunol. 1982 Jul;129(1):193-9
PMID: 6806358
-
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
-
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
-
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
-
A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity.
Anal Biochem. 1983 Jul 1;132(1):6-13
PMID: 6312838
-
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
-
Evolution of a multigene family of V kappa germ line genes.
EMBO J. 1984 Jan;3(1):185-91
PMID: 6546718
-
Idiotypic manipulations in the arsonate system.
Ann Immunol (Paris). 1984 Jan-Feb;135C(1):45-50
PMID: 6712161
-
Recurrent idiotopes and internal images.
EMBO J. 1982;1(2):243-7
PMID: 6985352
-
Junctional diversity is essential to antibody activity.
J Immunol. 1984 Sep;133(3):1090-2
PMID: 6747289
-
The generation of diversity in phosphorylcholine-binding antibodies.
Adv Immunol. 1984;35:1-37
PMID: 6431763
-
Molecular events during maturation of the immune response to oxazolone.
Nature. 1985 Aug 1-7;316(6027):412-8
PMID: 3927173
-
Regulation of genome rearrangement events during lymphocyte differentiation.
Immunol Rev. 1986 Feb;89:5-30
PMID: 3081433
-
Site-directed mutagenesis of an invariant amino acid residue at the variable-diversity segments junction of an antibody.
Proc Natl Acad Sci U S A. 1986 Apr;83(8):2628-31
PMID: 3085101
-
Sequences at the somatic recombination sites of immunoglobulin light-chain genes.
Nature. 1979 Jul 26;280(5720):288-94
PMID: 111144