Abstract
Somatic mutation occurs frequently in rearranged and expressed immunoglobulin variable region genes in vivo. In contrast, V region hypermutation seldom occurs in antibody-forming cells in culture. The S107 mouse myeloma cell line is one of the few cell lines that has been observed to generate V region mutations frequently and spontaneously in vitro. Detailed examination reveals that both the S107 tumor and the cell line derived from it contain and express a duplicated heavy-chain gene. In culture, only one of the two heavy-chain genes undergoes both V and C region mutation, and variants with complex phenotypes and genotypes arise as a result of mutation and segregation of these duplicated genes.
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Literature cited
Tonegawa, S. (1983).Nature 302575–581.
Alt, F.W., Blackwell, T.K., and Yancopolous, G.D. (1987).Science 2381079–1087.
Berek, C., and Milstein, C. (1988).Immunol. Rev. 1055–25.
French, D.L., Laskov, R., and Scharff, M.D. (1989).Science 2441152–1157.
Kochs, C., and Rajewsky, K. (1989).Annu. Rev. Immunol. 7537–559.
Rajewsky, K., Forster, I., and Cumano, A. (1987).Science 2381088–1094.
Morrison, S.L., and Scharff, M.D. (1981).CRC Crit. Rev. Immunol. 31–5.
Bruggermann, M., Radbruch, A., and Rajewsky, K. (1982).EMBO J. 1629–634.
Shulman, M.J., Husser, C., Filkin, C., and Kohler, G. (1982).Mol. Cell. Biol. 21033–1043.
Radbruch, A., Zaibs, S., Kappen, C., Bruggemann, M., Beyreuther, K., and Rajewsky, K. (1985).Nature 315506–508.
Panka, D.J., Mudgett-Hunter, M., Park, R.D., Peterson, L.L., Herzenberg, L.A., Haber, E., and Margolies, M.N. (1988).Proc. Natl. Acad. Sci. U.S.A. 853080–3084.
Wabl, M., Burrows, P.D., Von Gabair, A., and Steinberg, C. (1985).Proc. Natl. Acad. Sci. U.S.A. 82479–482.
Meyer, J., Jack, H.-M., Ellis, N., and Wabl, M. (1986).Proc. Natl. Acad. Sci. U.S.A. 836950–6953.
Jack, H.-M., and Wabl, M. (1987).Proc. Natl. Acad. Sci. U.S.A. 844935–4938.
Cohn, M., Notani, G., and Rice, S.A. (1969).Immunochemistry 6111.
Crews, S., Griffin, J., Haung, H., Calame, K., and Hood, L. (1981).Cell 2559–66.
Kohler, H. (1975).Transpl. Rec. 2724–56.
Briles, D.E., Forman, C., Hodak, S., and Claflin, J.L. (1982).J. Exp. Med. 1561177–1185.
Kwan, S.-P., Rudikoff, S., Seidman, J.G., Leder, P., and Scharff, M.D. (1981)J. Exp. Med. 1531366–1370.
Gearhart, P.J., Johnson, N.D., Douglas, R., and Hood, L. (1981).Nature 29129–34.
Satow, Y., Cohen, G.H., Padlan, E.A., and Davies, D.R. (1986).J. Mol. Biol. 190593–604.
Cook, W.D., and Scharff, M.D. (1977).Proc. Natl. Acad. Sci. U.S.A. 745687–5691.
Giusti, A., Chein, N.C., Zack, D., Shin, S.-U., and Scharff, M.D. (1987).Proc. Natl. Acad. Sci. U.S.A. 842926–2930.
Diamond, B., and Scharff, M.D. (1984).Proc. Natl. Acad. Sci. U.S.A. 815841–5844.
Chien, N.C., Roberts, V.A., Giusti, A.M., Scharff, M.D., and Getzoff, E.D. (1989).Proc. Natl. Acad. Sci. U.S.A. 865532–5536.
Cook, W.D., Rudikoff, S., Giusti, A.M., and Scharff, M.D. (1982).Proc. Natl. Acad. Sci. U.S.A. 791240–1244.
Rudikoff, S., Giusti, A.M., Cook, W.D., and Scharff, M.D. (1982).Proc. Natl. Acad. Sci. U.S.A. 791979–1983.
Chien, N.C., Pollock, R.R., Desaymard, C., and Scharff, M.D. (1988).J. Exp. Med. 167954–973.
Soeiro, R., and Darnell, J.E. (1969).J. Mol. Biol. 44551–562.
Thomas, P.S. (1980).Proc. Natl. Acad. Sci. U.S.A. 775201–5205.
Zeff, R.A., Gopas, J., Steinhauer, E., Rajan, T.V., and Nathenson, S.G. (1986).J. Immunol. 137897–903.
Pease, L.R., Nathenson, S.G., and Leinwand, L.A. (1982).Nature 298382–385.
Wickens, M.P., Buell, G.N., and Schimke, R.T. (1978).J. Biol. Chem. 2532483–2485.
Buell, G.N., Wickens, M.P., Paguar, F., and Schimke, R.T. (1978).J. Biol. Chem. 2532483–2495.
Sanger, F., Micklen, S., and Coulson, A.R. (1977).Proc. Natl. Acad. Sci. U.S.A. 705403–5467.
Geliebter, J. (1987).Focus 91–8.
Sanger, F., and Coulson, A.R. (1978).FEBS Lett. 87107–110.
Cook, W.D. (1979). Antigen binding variants in the mouse myeloma cell line. Doctoral dissertation. Albert Einstein College of Medicine, Yeshiva University, New York.
Zack, D.J., Morrison, S.L., Cook, W.D., Dackowski, W., and Scharff, M.D. (1981).J. Exp. Med. 1541554–1569.
Behar, S.M., Chien, N.C., Corbet, S., Diamond, B.A., Getzoff, E.D., Lustgarten, D., Roberts, V., Scharff, M.D., and Shin, S.-U. (1989). Cold Spring Harbor Symp. Quant. Biol.54921–931.
Bauman, B., Potash, M.J., and Kohler, G. (1985).EMBO J. 4351–359.
Kwan, S.-P., Max, E.E., Seidman, J.G., Leder, P., and Scharff, M.D. (1981).Cell 2657–66.
Zack, D.J. (1984). Doctoral dissertation. Albert Einstein College of Medicine, Yeshiva University, New York.
Golding, G.B., Gearhart, P.J., and Glickman, B.W. (1987).Genetics 115169–176.
Gross, M.D., and Siegel, E.C. (1981).Mutat. Res. 91107.
Hackett, J.J., Rogerson, R.J., O'Brien, R.L., and Storb, U. (1990).J. Exp. Med. 172135–137.
Leder, P., Honjo, T., Seidman, T., and Swan, D. (1976). Cold Spring Harbor Symp. Quant. Biol.41855.
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Shin, SU., DePinho, R., Zack, D.J. et al. Instability of immunoglobulin genes in S107 cell line. Somat Cell Mol Genet 17, 259–276 (1991). https://doi.org/10.1007/BF01232821
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DOI: https://doi.org/10.1007/BF01232821