Affinity maturation leads to differential expression of multiple copies of a kappa light-chain transgene - PubMed (original) (raw)
. 1993 May 20;363(6426):271-3.
doi: 10.1038/363271a0.
Affiliations
- PMID: 8487865
- DOI: 10.1038/363271a0
Affinity maturation leads to differential expression of multiple copies of a kappa light-chain transgene
F Lozano et al. Nature. 1993.
Erratum in
- Nature 1995 Mar 2;374(6517):94
Abstract
Transgenic animals containing rearranged heavy or light chains are used to study the process of hypermutation, which characterizes the maturation of the antibody response. LK6 mice contain five copies of a transgene coding for a light chain produced in response to the hapten 2-phenyloxazolone. We have selected hybridomas from secondary responses that express the transgene as the only light chain. Some of these hybridomas contain transgene copies carrying mutations known to improve antibody affinity. We have analysed the expression of the five transgene copies in those hybridomas. We report here that the somatic hypermutation process can affect the successful expression of antibody light-chain transgenes. When mutations that improve the antibody affinity appear in one transgene copy, antigenic selection favours cells that downregulate the other copies at multiple levels of gene expression, including examples where nonsense mutations correlate with a drop in messenger RNA level.
Comment in
- Immunology. The power of clonal selection.
Rajewsky K. Rajewsky K. Nature. 1993 May 20;363(6426):208. doi: 10.1038/363208a0. Nature. 1993. PMID: 8487859 No abstract available.
Similar articles
- Lack of somatic mutation in a kappa light chain transgene.
Sharpe MJ, Neuberger M, Pannell R, Surani MA, Milstein C. Sharpe MJ, et al. Eur J Immunol. 1990 Jun;20(6):1379-85. doi: 10.1002/eji.1830200625. Eur J Immunol. 1990. PMID: 2115000 - Influence of a V kappa 8 L chain transgene on endogenous rearrangements and the immune response to the HA(Sb) determinant on influenza virus.
Carmack CE, Camper SA, Mackle JJ, Gerhard WU, Weigert MG. Carmack CE, et al. J Immunol. 1991 Sep 15;147(6):2024-33. J Immunol. 1991. PMID: 1909739 - Analysis of hypermutation in immunoglobulin heavy chain passenger transgenes.
Johnston JM, Ihyer SR, Smith RS, Tai KF, Farmer T, Korsmeyer SJ, Nadon NL, Carroll WL. Johnston JM, et al. Eur J Immunol. 1996 May;26(5):1058-62. doi: 10.1002/eji.1830260515. Eur J Immunol. 1996. PMID: 8647167 - Somatic hypermutation of an immunoglobulin transgene in kappa transgenic mice.
O'Brien RL, Brinster RL, Storb U. O'Brien RL, et al. Nature. 1987 Mar 26-Apr 1;326(6111):405-9. doi: 10.1038/326405a0. Nature. 1987. PMID: 3104790 - Antibody repertoires of four- and five-feature translocus mice carrying human immunoglobulin heavy chain and kappa and lambda light chain yeast artificial chromosomes.
Nicholson IC, Zou X, Popov AV, Cook GP, Corps EM, Humphries S, Ayling C, Goyenechea B, Xian J, Taussig MJ, Neuberger MS, Brüggemann M. Nicholson IC, et al. J Immunol. 1999 Dec 15;163(12):6898-906. J Immunol. 1999. PMID: 10586092
Cited by
- Analysis of the Structural Dynamics of Proteins in the Ligand-Unbound and -Bound States by Diffracted X-ray Tracking.
Oda M. Oda M. Int J Mol Sci. 2023 Sep 6;24(18):13717. doi: 10.3390/ijms241813717. Int J Mol Sci. 2023. PMID: 37762021 Free PMC article. Review. - The 7-valent pneumococcal conjugate vaccine elicits cross-functional opsonophagocytic killing responses to Streptococcus pneumoniae serotype 6D in children.
Lee H, Cha JH, Nahm MH, Burton RL, Kim KH. Lee H, et al. BMC Infect Dis. 2013 Oct 10;13:474. doi: 10.1186/1471-2334-13-474. BMC Infect Dis. 2013. PMID: 24112237 Free PMC article. - IgG1+ ovalbumin-specific B-cell transnuclear mice show class switch recombination in rare allelically included B cells.
Dougan SK, Ogata S, Hu CC, Grotenbreg GM, Guillen E, Jaenisch R, Ploegh HL. Dougan SK, et al. Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13739-44. doi: 10.1073/pnas.1210273109. Epub 2012 Aug 6. Proc Natl Acad Sci U S A. 2012. PMID: 22869725 Free PMC article. - Allelic exclusion of immunoglobulin genes: models and mechanisms.
Vettermann C, Schlissel MS. Vettermann C, et al. Immunol Rev. 2010 Sep;237(1):22-42. doi: 10.1111/j.1600-065X.2010.00935.x. Immunol Rev. 2010. PMID: 20727027 Free PMC article. Review. - Altered spectra of hypermutation in antibodies from mice deficient for the DNA mismatch repair protein PMS2.
Winter DB, Phung QH, Umar A, Baker SM, Tarone RE, Tanaka K, Liskay RM, Kunkel TA, Bohr VA, Gearhart PJ. Winter DB, et al. Proc Natl Acad Sci U S A. 1998 Jun 9;95(12):6953-8. doi: 10.1073/pnas.95.12.6953. Proc Natl Acad Sci U S A. 1998. PMID: 9618520 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources