Abstract
The B-cell repertoire in neonatal mice contains predominant clonotypes that are reproducibly expressed at particular times after birth. We have isolated and sequenced heavy and light chain cDNA clones from three 2,4-dinitrophenyl-specific neonatal hybridomas. Two of these hybridomas (TF2-36 and TF5-139) express idiotypes (Ids) that predominate during the first days after birth, and the third hybridoma (TF2-76) expresses an Id that predominates during the second week after birth. The heavy (H) chain variable (V) region of the TF2-76 hybridoma protein is encoded by a member of the 7183 VH family, one of eight families of murine VH genes that have been defined by Brodeur and Riblet [Brodeur, P. H. & Riblet, R. (1984) Eur. J. Immunol. 14, 922-930]. Members of this family have been found to undergo a disproportionately high frequency of rearrangement in fetal and neonatal liver pre-B-cells. Because the 7183 VH family is located close to the H chain joining (J) region gene segments, JH, other workers have proposed that VH rearrangement frequency is related to distance from the JH segments. However, the two earlier-appearing predominant clonotypes expressed by TF2-36 and TF5-139 hybridoma proteins utilize a member of the 36-60 VH family, probably VH 1210.7, which is located distal to the JH gene segments on chromosome 12. Since 20-30% of day 3 dinitrophenyl-specific B cells express either the Id(TF2-36) or the Id(TF5-139), the VH 1210.7 gene must be utilized at high frequency early in development. These results indicate that the utilization of rearranged VH segments is strongly influenced by factors other than distance from JH.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Auffray C., Nageotte R., Sikorav J. L., Heidmann O., Rougeon F. Mouse immunoglobulin A: nucleotide sequence of the structural gene for the alpha heavy chain derived from cloned cDNAs. Gene. 1981 May;13(4):365–374. doi: 10.1016/0378-1119(81)90016-0. [DOI] [PubMed] [Google Scholar]
- Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barstad P., Hubert J., Hunkapiller M., Goetze A., Schilling J., Black B., Eaton B., Richards J., Weigert M., Hood L. Immunoglobulins with hapten-binding activity: structure-function correlations and genetic implications. Eur J Immunol. 1978 Jul;8(7):497–503. doi: 10.1002/eji.1830080709. [DOI] [PubMed] [Google Scholar]
- Biggin M. D., Gibson T. J., Hong G. F. Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963–3965. doi: 10.1073/pnas.80.13.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bona C., Mond J. J., Stein K. E., House S., Lieberman R., Paul W. E. Immune response to levan. III. The capacity to produce anti-inulin antibodies and cross-reactive idiotypes appears late in ontogeny. J Immunol. 1979 Oct;123(4):1484–1490. [PubMed] [Google Scholar]
- Brodeur P. H., Riblet R. The immunoglobulin heavy chain variable region (Igh-V) locus in the mouse. I. One hundred Igh-V genes comprise seven families of homologous genes. Eur J Immunol. 1984 Oct;14(10):922–930. doi: 10.1002/eji.1830141012. [DOI] [PubMed] [Google Scholar]
- Cancro M. P., Wylie D. E., Gerhard W., Klinman N. R. Patterned acquisition of the antibody repertoire: diversity of the hemagglutinin-specific B-cell repertoire in neonatal BALB/c mice. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6577–6581. doi: 10.1073/pnas.76.12.6577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Casadaban M. J., Cohen S. N. Analysis of gene control signals by DNA fusion and cloning in Escherichia coli. J Mol Biol. 1980 Apr;138(2):179–207. doi: 10.1016/0022-2836(80)90283-1. [DOI] [PubMed] [Google Scholar]
- Denis K. A., Klinman N. R. Genetic and temporal control of neonatal antibody expression. J Exp Med. 1983 Apr 1;157(4):1170–1183. doi: 10.1084/jem.157.4.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fernandez C., Möller G. Immunological unresponsiveness to native dextran B512 in young animals of dextran high responder strains is due to lack of Ig receptors expression. Evidence for a nonrandom expression of V-genes. J Exp Med. 1978 Mar 1;147(3):645–655. doi: 10.1084/jem.147.3.645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fung J., Köhler H. Late clonal selection and expansion of the TEPC-15 germ-line specificity. J Exp Med. 1980 Nov 1;152(5):1262–1273. doi: 10.1084/jem.152.5.1262. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gopinathan K. P., Weymouth L. A., Kunkel T. A., Loeb L. A. Mutagenesis in vitro by DNA polymerase from an RNA tumour virus. Nature. 1979 Apr 26;278(5707):857–859. doi: 10.1038/278857a0. [DOI] [PubMed] [Google Scholar]
- Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [DOI] [PubMed] [Google Scholar]
- Hewick R. M., Hunkapiller M. W., Hood L. E., Dreyer W. J. A gas-liquid solid phase peptide and protein sequenator. J Biol Chem. 1981 Aug 10;256(15):7990–7997. [PubMed] [Google Scholar]
- Hunkapiller M. W., Lujan E., Ostrander F., Hood L. E. Isolation of microgram quantities of proteins from polyacrylamide gels for amino acid sequence analysis. Methods Enzymol. 1983;91:227–236. doi: 10.1016/s0076-6879(83)91019-4. [DOI] [PubMed] [Google Scholar]
- Kawakami T., Takahashi N., Honjo T. Complete nucleotide sequence of mouse immunoglobulin mu gene and comparison with other immunoglobulin heavy chain genes. Nucleic Acids Res. 1980 Sep 11;8(17):3933–3945. doi: 10.1093/nar/8.17.3933. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klinman N. R., Press J. L. The B cell specificity repertoire: its relationship to definable subpopulations. Transplant Rev. 1975;24:41–83. doi: 10.1111/j.1600-065x.1975.tb00165.x. [DOI] [PubMed] [Google Scholar]
- Klinman N. R., Press J. L. The characterization fo the B-cell repertoire specific for the 2,4-dinitrophenyl and 2,4,6-trinitrophenyl determinants in neonatal BALB/c mice. J Exp Med. 1975 May 1;141(5):1133–1146. doi: 10.1084/jem.141.5.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kraig E., Kronenberg M., Kapp J. A., Pierce C. W., Abruzzini A. F., Sorensen C. M., Samelson L. E., Schwartz R. H., Hood L. E. 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. doi: 10.1084/jem.158.1.192. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurosawa Y., Tonegawa S. Organization, structure, and assembly of immunoglobulin heavy chain diversity DNA segments. J Exp Med. 1982 Jan 1;155(1):201–218. doi: 10.1084/jem.155.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lazure C., Hum W. T., Gibson D. M. Sequence diversity within a subgroup of mouse immunoglobulin kappa chains controlled by the IgK-Ef2 locus. J Exp Med. 1981 Jul 1;154(1):146–155. doi: 10.1084/jem.154.1.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marcu K. B., Schibler U., Perry R. P. Nuclear transcripts of mouse heavy chain immunoglobulin genes contain only the expressed class of C-region sequences. Science. 1979 Jun 8;204(4397):1087–1088. doi: 10.1126/science.109919. [DOI] [PubMed] [Google Scholar]
- Max E. E., Seidman J. G., Leder P. Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3450–3454. doi: 10.1073/pnas.76.7.3450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maxam A. M., Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. doi: 10.1016/s0076-6879(80)65059-9. [DOI] [PubMed] [Google Scholar]
- Near R. I., Juszczak E. C., Huang S. Y., Sicari S. A., Margolies M. N., Gefter M. L. Expression and rearrangement of homologous immunoglobulin VH genes in two mouse strains. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2167–2171. doi: 10.1073/pnas.81.7.2167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perlmutter R. M., Kearney J. F., Chang S. P., Hood L. E. Developmentally controlled expression of immunoglobulin VH genes. Science. 1985 Mar 29;227(4694):1597–1601. doi: 10.1126/science.3975629. [DOI] [PubMed] [Google Scholar]
- Pernis B., Chiappino G., Kelus A. S., Gell P. G. Cellular localization of immunoglobulins with different allotypic specificities in rabbit lymphoid tissues. J Exp Med. 1965 Nov 1;122(5):853–876. doi: 10.1084/jem.122.5.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rudikoff S., Pawlita M., Pumphrey J., Heller M. Somatic diversification of immunoglobulins. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2162–2166. doi: 10.1073/pnas.81.7.2162. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rudikoff S., Satow Y., Padlan E., Davies D., Potter M. Kappa chain structure from a crystallized murine Fab': role of joining segment in hapten binding. Mol Immunol. 1981 Aug;18(8):705–711. doi: 10.1016/0161-5890(81)90062-6. [DOI] [PubMed] [Google Scholar]
- SILVERSTEIN A. M., UHR J. W., KRANER K. L., LUKES R. J. Fetal response to antigenic stimulus. II. Antibody production by the fetal lamb. J Exp Med. 1963 May 1;117:799–812. doi: 10.1084/jem.117.5.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sakano H., Hüppi K., Heinrich G., Tonegawa S. Sequences at the somatic recombination sites of immunoglobulin light-chain genes. Nature. 1979 Jul 26;280(5720):288–294. doi: 10.1038/280288a0. [DOI] [PubMed] [Google Scholar]
- Sakano H., Maki R., Kurosawa Y., Roeder W., Tonegawa S. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature. 1980 Aug 14;286(5774):676–683. doi: 10.1038/286676a0. [DOI] [PubMed] [Google Scholar]
- Seidman J. G., Leder P. The arrangement and rearrangement of antibody genes. Nature. 1978 Dec 21;276(5690):790–795. doi: 10.1038/276790a0. [DOI] [PubMed] [Google Scholar]
- Sherwin W. K., Rowlands D. T., Jr Development of humoral immunity in lethally irradiated mice reconstituted with fetal liver. J Immunol. 1974 Oct;113(4):1353–1360. [PubMed] [Google Scholar]
- Shulman M., Wilde C. D., Köhler G. A better cell line for making hybridomas secreting specific antibodies. Nature. 1978 Nov 16;276(5685):269–270. doi: 10.1038/276269a0. [DOI] [PubMed] [Google Scholar]
- Sigal N. H., Gearhart P. J., Press J. L., Klinman N. R. Late acquisition of a germ line antibody specificity. Nature. 1976 Jan 1;259(5538):51–52. doi: 10.1038/259051a0. [DOI] [PubMed] [Google Scholar]
- Stohrer R., Kearney J. Ontogeny of B cell precursors responding to alpha 1- greater than 3 dextran in BALB/c mice. J Immunol. 1984 Nov;133(5):2323–2326. [PubMed] [Google Scholar]
- Strohman R. C., Moss P. S., Micou-Eastwood J., Spector D., Przybyla A., Paterson B. Messenger RNA for myosin polypeptides: isolation from single myogenic cell cultures. Cell. 1977 Feb;10(2):265–273. doi: 10.1016/0092-8674(77)90220-3. [DOI] [PubMed] [Google Scholar]
- Yancopoulos G. D., Desiderio S. V., Paskind M., Kearney J. F., Baltimore D., Alt F. W. Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines. Nature. 1984 Oct 25;311(5988):727–733. doi: 10.1038/311727a0. [DOI] [PubMed] [Google Scholar]