Abstract
A few percent of mouse splenocytes express isotypes characteristic of the secondary response together with IgM, and some cells express these isotypes alone. We isolated populations of small memory cells that express (i) IgM but not IgG1, (ii) IgM but not IgA, (iii) IgM and IgG1, (iv) IgM and IgA, and (v) IgG1 but not IgM. We have analyzed their DNA to show that there has been no switch recombination or deletion in the Ig constant region (C) genes. Using sandwich RNA hybridizations, we have found that cells expressing IgG1 contain nuclear RNAs that have both C mu and C gamma 1 sequences, and that cells expressing IgA contain nuclear RNAs that have both C mu and C alpha sequences. We propose that the expression of an isotype characteristic of the secondary response in memory cells is accomplished by alternative RNA processing of large (up to 180 kilobases) nuclear RNA transcripts that span the heavy chain gene locus.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alt F. W., Bothwell A. L., Knapp M., Siden E., Mather E., Koshland M., Baltimore D. Synthesis of secreted and membrane-bound immunoglobulin mu heavy chains is directed by mRNAs that differ at their 3' ends. Cell. 1980 Jun;20(2):293–301. doi: 10.1016/0092-8674(80)90615-7. [DOI] [PubMed] [Google Scholar]
- Cate R. L., Chick W., Gilbert W. Comparison of the methylation patterns of the two rat insulin genes. J Biol Chem. 1983 May 25;258(10):6645–6652. [PubMed] [Google Scholar]
- Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cory S., Adams J. M. Deletions are associated with somatic rearrangement of immunoglobulin heavy chain genes. Cell. 1980 Jan;19(1):37–51. doi: 10.1016/0092-8674(80)90386-4. [DOI] [PubMed] [Google Scholar]
- Denhardt D. T. A membrane-filter technique for the detection of complementary DNA. Biochem Biophys Res Commun. 1966 Jun 13;23(5):641–646. doi: 10.1016/0006-291x(66)90447-5. [DOI] [PubMed] [Google Scholar]
- Dunn A. R., Sambrook J. Mapping viral mRNAs by sandwich hybridization. Methods Enzymol. 1980;65(1):468–478. doi: 10.1016/s0076-6879(80)65056-3. [DOI] [PubMed] [Google Scholar]
- Early P., Huang H., Davis M., Calame K., Hood L. An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH. Cell. 1980 Apr;19(4):981–992. doi: 10.1016/0092-8674(80)90089-6. [DOI] [PubMed] [Google Scholar]
- Kataoka T., Kawakami T., Takahashi N., Honjo T. Rearrangement of immunoglobulin gamma 1-chain gene and mechanism for heavy-chain class switch. Proc Natl Acad Sci U S A. 1980 Feb;77(2):919–923. doi: 10.1073/pnas.77.2.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laskey R. A., Mills A. D. Enhanced autoradiographic detection of 32P and 125I using intensifying screens and hypersensitized film. FEBS Lett. 1977 Oct 15;82(2):314–316. doi: 10.1016/0014-5793(77)80609-1. [DOI] [PubMed] [Google Scholar]
- Lomedico P. T., Saunders G. F. Preparation of pancreatic mRNA: cell-free translation of an insulin-immunoreactive polypeptide. Nucleic Acids Res. 1976 Feb;3(2):381–391. doi: 10.1093/nar/3.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maki R., Roeder W., Traunecker A., Sidman C., Wabl M., Raschke W., Tonegawa S. The role of DNA rearrangement and alternative RNA processing in the expression of immunoglobulin delta genes. Cell. 1981 May;24(2):353–365. doi: 10.1016/0092-8674(81)90325-1. [DOI] [PubMed] [Google Scholar]
- Maki R., Traunecker A., Sakano H., Roeder W., Tonegawa S. Exon shuffling generates an immunoglobulin heavy chain gene. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2138–2142. doi: 10.1073/pnas.77.4.2138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore K. W., Rogers J., Hunkapiller T., Early P., Nottenburg C., Weissman I., Bazin H., Wall R., Hood L. E. Expression of IgD may use both DNA rearrangement and RNA splicing mechanisms. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1800–1804. doi: 10.1073/pnas.78.3.1800. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nikaido T., Yamawaki-Kataoka Y., Honjo T. Nucleotide sequences of switch regions of immunoglobulin C epsilon and C gamma genes and their comparison. J Biol Chem. 1982 Jul 10;257(13):7322–7329. [PubMed] [Google Scholar]
- Nottenburg C., Weissman I. L. Cmu gene rearrangement of mouse immunoglobulin genes in normal B cells occurs on both the expressed and nonexpressed chromosomes. Proc Natl Acad Sci U S A. 1981 Jan;78(1):484–488. doi: 10.1073/pnas.78.1.484. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okumura K., Julius M. H., Tsu T., Herzenberg L. A., Herzenberg L. A. Demonstration that IgG memory is carried by IgG-bearing cells. Eur J Immunol. 1976 Jul;6(7):467–472. doi: 10.1002/eji.1830060704. [DOI] [PubMed] [Google Scholar]
- Rabbitts T. H., Forster A., Dunnick W., Bentley D. L. The role of gene deletion in the immunoglobulin heavy chain switch. Nature. 1980 Jan 24;283(5745):351–356. doi: 10.1038/283351a0. [DOI] [PubMed] [Google Scholar]
- Radbruch A., Sablitzky F. Deletion of Cmu genes in mouse B lymphocytes upon stimulation with LPS. EMBO J. 1983;2(11):1929–1935. doi: 10.1002/j.1460-2075.1983.tb01681.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rogers J., Early P., Carter C., Calame K., Bond M., Hood L., Wall R. Two mRNAs with different 3' ends encode membrane-bound and secreted forms of immunoglobulin mu chain. Cell. 1980 Jun;20(2):303–312. doi: 10.1016/0092-8674(80)90616-9. [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]
- Schibler U., Marcu K. B., Perry R. P. The synthesis and processing of the messenger RNAs specifying heavy and light chain immunoglobulins in MPC-11 cells. Cell. 1978 Dec;15(4):1495–1509. doi: 10.1016/0092-8674(78)90072-7. [DOI] [PubMed] [Google Scholar]
- Shimizu A., Honjo T. Immunoglobulin class switching. Cell. 1984 Apr;36(4):801–803. doi: 10.1016/0092-8674(84)90029-1. [DOI] [PubMed] [Google Scholar]
- Shimizu A., Takahashi N., Yaoita Y., Honjo T. Organization of the constant-region gene family of the mouse immunoglobulin heavy chain. Cell. 1982 Mar;28(3):499–506. doi: 10.1016/0092-8674(82)90204-5. [DOI] [PubMed] [Google Scholar]
- Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
- Wu C. The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature. 1980 Aug 28;286(5776):854–860. doi: 10.1038/286854a0. [DOI] [PubMed] [Google Scholar]
- Yaoita Y., Kumagai Y., Okumura K., Honjo T. Expression of lymphocyte surface IgE does not require switch recombination. Nature. 1982 Jun 24;297(5868):697–699. doi: 10.1038/297697a0. [DOI] [PubMed] [Google Scholar]