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. 1993 May 1;90(9):4008–4011. doi: 10.1073/pnas.90.9.4008

Increasing the chemical potential of the germ-line antibody repertoire.

N Sarvetnick 1, D Gurushanthaiah 1, N Han 1, J Prudent 1, P Schultz 1, R Lerner 1
PMCID: PMC46435  PMID: 8483917

Abstract

To augment the chemical potential of the immunological repertoire, a metal ion-binding light chain has been introduced into the murine genome. Mice containing the transgene were subsequently immunized with a fluorescein conjugate. The transgenic light chain was found at a high frequency in the anti-fluorescein memory B-cell compartment. This general method should be applicable to other cofactors and small molecules and should lead to generation of antibodies with unique catalytic activities.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barbas C. F., 3rd, Bain J. D., Hoekstra D. M., Lerner R. A. Semisynthetic combinatorial antibody libraries: a chemical solution to the diversity problem. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4457–4461. doi: 10.1073/pnas.89.10.4457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bird R. E., Hardman K. D., Jacobson J. W., Johnson S., Kaufman B. M., Lee S. M., Lee T., Pope S. H., Riordan G. S., Whitlow M. Single-chain antigen-binding proteins. Science. 1988 Oct 21;242(4877):423–426. doi: 10.1126/science.3140379. [DOI] [PubMed] [Google Scholar]
  3. Brinster R. L., Ritchie K. A., Hammer R. E., O'Brien R. L., Arp B., Storb U. Expression of a microinjected immunoglobulin gene in the spleen of transgenic mice. Nature. 1983 Nov 24;306(5941):332–336. doi: 10.1038/306332a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brombacher F., Köhler G., Eibel H. B cell tolerance in mice transgenic for anti-CD8 immunoglobulin mu chain. J Exp Med. 1991 Dec 1;174(6):1335–1346. doi: 10.1084/jem.174.6.1335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Carmack C. E., Camper S. A., Mackle J. J., Gerhard W. U., Weigert M. G. Influence of a V kappa 8 L chain transgene on endogenous rearrangements and the immune response to the HA(Sb) determinant on influenza virus. J Immunol. 1991 Sep 15;147(6):2024–2033. [PubMed] [Google Scholar]
  6. Erikson J., Radic M. Z., Camper S. A., Hardy R. R., Carmack C., Weigert M. Expression of anti-DNA immunoglobulin transgenes in non-autoimmune mice. Nature. 1991 Jan 24;349(6307):331–334. doi: 10.1038/349331a0. [DOI] [PubMed] [Google Scholar]
  7. Hartley S. B., Crosbie J., Brink R., Kantor A. B., Basten A., Goodnow C. C. Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens. Nature. 1991 Oct 24;353(6346):765–769. doi: 10.1038/353765a0. [DOI] [PubMed] [Google Scholar]
  8. Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
  9. Iverson B. L., Iverson S. A., Roberts V. A., Getzoff E. D., Tainer J. A., Benkovic S. J., Lerner R. A. Metalloantibodies. Science. 1990 Aug 10;249(4969):659–662. doi: 10.1126/science.2116666. [DOI] [PubMed] [Google Scholar]
  10. Lerner R. A., Benkovic S. J., Schultz P. G. At the crossroads of chemistry and immunology: catalytic antibodies. Science. 1991 May 3;252(5006):659–667. doi: 10.1126/science.2024118. [DOI] [PubMed] [Google Scholar]
  11. McDonnell T. J., Deane N., Platt F. M., Nunez G., Jaeger U., McKearn J. P., Korsmeyer S. J. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 1989 Apr 7;57(1):79–88. doi: 10.1016/0092-8674(89)90174-8. [DOI] [PubMed] [Google Scholar]
  12. O'Brien R. L., Brinster R. L., Storb U. Somatic hypermutation of an immunoglobulin transgene in kappa transgenic mice. 1987 Mar 26-Apr 1Nature. 326(6111):405–409. doi: 10.1038/326405a0. [DOI] [PubMed] [Google Scholar]
  13. Okamoto M., Murakami M., Shimizu A., Ozaki S., Tsubata T., Kumagai S., Honjo T. A transgenic model of autoimmune hemolytic anemia. J Exp Med. 1992 Jan 1;175(1):71–79. doi: 10.1084/jem.175.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Reinitz D. M., Voss E. W., Jr Identification of recurrent idiotypes within the unrestricted anti-fluorescein immune response. J Immunol. 1985 Nov;135(5):3365–3371. [PubMed] [Google Scholar]
  15. Ritchie K. A., Brinster R. L., Storb U. Allelic exclusion and control of endogenous immunoglobulin gene rearrangement in kappa transgenic mice. Nature. 1984 Dec 6;312(5994):517–520. doi: 10.1038/312517a0. [DOI] [PubMed] [Google Scholar]
  16. Strasser A., Whittingham S., Vaux D. L., Bath M. L., Adams J. M., Cory S., Harris A. W. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8661–8665. doi: 10.1073/pnas.88.19.8661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Vaux D. L., Cory S., Adams J. M. Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature. 1988 Sep 29;335(6189):440–442. doi: 10.1038/335440a0. [DOI] [PubMed] [Google Scholar]
  18. Watanabe-Fukunaga R., Brannan C. I., Copeland N. G., Jenkins N. A., Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992 Mar 26;356(6367):314–317. doi: 10.1038/356314a0. [DOI] [PubMed] [Google Scholar]

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