Abstract
SOMATIC hypermutation and affinity-driven selection of active immunoglobulin genes occur in germinal centres (GCs), resulting in the generation of high-affinity memory B cells1–3. In contrast, T lymphocytes do not require the germinal centre microenviron-ment to establish memory4 and the T-cell antigen receptor (TCR) genes, though homologous to immunoglobulin genes, are believed to be incapable of hypermutation5–7. Here we present direct evidence that the small population of antigen-specific T cells that are recruited into splenic GCs acquire mutations in the variable region of genes encoding TCR α-chains (Vα) but not those of β-chains. These locus-specific mutations reach frequencies comparable to mutated immunoglobulin VH exons recovered from the same site and exhibit similar substitution biases and DNA strand polarity. T cells bearing identical mutations appear in multiple GCs, raising the possibility that some cells bearing mutant TCRs may re-enter the peripheral lymphocyte pool.
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References
Allen, D., Simon, T., Sablitzky, F., Rajewsky, K. & Cumano, A. EMBO J. 7, 1995–2001 (1988).
Weiss, U. & Rajewsky, K. J. exp. Med. 172, 1680–1689 (1990).
Jacob, J., Kelsoe, G., Rajewsky, K. & Weiss, U. Nature 354, 389–392 (1991).
Lane, P. et al. J. exp. Med. 179, 819–830 (1994).
Davis, M. M. & Bjorkman, P. Nature 334, 395–402 (1988).
Vitetta, E. S. et al. A. Rev. Immun. 9, 193–217 (1991).
Hackett, J. et al. J. exp. Med. 176, 225–231 (1992).
Winoto, A. et al. Nature 324, 679–682 (1986).
Cumano, A. & Rajewsky, K. EMBO J. 5, 2459–2468 (1986).
Tao, W. & Bothwell, A. L M. J. Immun. 145, 3216–3222 (1990).
Jacob, J. & Kelsoe, G. J. exp. Med. 176, 678–687 (1992).
Kelsoe, G. & Zheng, B. Curr. Opin. Immun. 5, 418–422 (1993).
Jacob, J., Przylepa, J., Miller C. & Kelsoe, G. J. exp. Med. 178, 1293–1307 (1993).
Kuppers, R., Zhao, M., Hansmann, M.-L. & Rajewsky, K. EMBO J. 12, 4955–4967 (1993).
Fuller, K., Kanagawa, O. & Nahm, M. H. J. Immun. 9, 4505–4512 (1993).
Sprent, J. Cell 76, 315–322 (1994).
Becker, D. et al. Nature 317, 430–434 (1985).
Hayday, A. C. et al. Nature 316, 828–832 (1985).
Chien, Y-H. et al. Nature 309, 322–326 (1984).
Bernard, O., Hozumi, N. & Tonegawa, S. Cell 15, 1133–1144 (1978).
Blomberg, B. & Tonegawa, S. Proc. natn. Acad. Sci. U.S.A. 79, 530–533 (1982).
Lundberg, K. S. et al. Gene 108, 1–6 (1991).
Fink, P. J., Matis, L. A., McElligott, D. L., Bookman, M. & Hedrick, S. M. Nature 321, 219–226 (1986).
Padovan, E. et al. Science 262, 422–424 (1993).
MacLennan, I. C. M. A. Rev. Immun. 12, 117–139 (1994).
Lebecque, S. & Gearhart, P. J. exp. Med. 172, 1717–1727 (1990).
Betz, A., Neuberger, M. S. & Milstein, C. Immun. Today 14, 405–411 (1993).
Malissen, M. et al. Cell 5, 49–59 (1988).
Zoller, M. & Smith, M. Nucleic Acids Res. 10, 6487–6500 (1982).
Okada, A., Mendelsohn, M. & Alt, F. J. exp. Med. 180, 261–272 (1994).
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Zheng, B., Xue, W. & Kelsoe, G. Locus-specific somatic hypermutation in germinal centre T cells. Nature 372, 556–559 (1994). https://doi.org/10.1038/372556a0
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DOI: https://doi.org/10.1038/372556a0
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