Maintenance of Serological Memory by Polyclonal Activation of Human Memory B Cells
Abstract
Production of antibodies can last for a lifetime, through mechanisms that remain poorly understood. Here, we show that human memory B lymphocytes proliferate and differentiate into plasma cells in response to polyclonal stimuli, such as bystander T cell help and CpG DNA. Furthermore, plasma cells secreting antibodies to recall antigens are produced in vivo at levels proportional to the frequency of specific memory B cells, even several years after antigenic stimulation. Although antigen boosting leads to a transient increase in specific antibody levels, ongoing polyclonal activation of memory B cells offers a means to maintain serological memory for a human lifetime.
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REFERENCES AND NOTES
1
Rajewsky K., Nature 381, 751 (1996).
2
Banchereau J., et al., Annu. Rev. Immunol. 12, 881 (1994).
3
Maruyama M., Lam K. P., Rajewsky K., Nature 407, 636 (2000).
4
Manz R. A., Thiel A., Radbruch A., Nature 388, 133 (1997).
5
Slifka M. K., Antia R., Whitmire J. K., Ahmed R., Immunity 8, 363 (1998).
6
Ahmed R., Gray D., Science 272, 54 (1996).
7
Manz R. A., et al., Curr. Opin. Immunol. 14, 517 (2002).
8
Zinkernagel R. M., Curr. Opin. Immunol. 14, 523 (2002).
9
Ochsenbein A. F., et al., Proc. Natl. Acad. Sci. U.S.A. 97, 13263 (2000).
10
Poltorak A., et al., Science 282, 20 (1998).
11
Krieg A. M., Annu. Rev. Immunol. 20, 709 (2002).
12
Lanzavecchia A., Eur. J. Immunol. 13, 820 (1983).
13
Klein U., Rajewsky K., Kuppers R., J. Exp. Med. 188, 1679 (1998).
14
See supporting data on Science Online.
15
N. L. Bernasconi, E. Traggiai, unpublished data.
16
Ansel K. M., et al., J. Exp. Med. 190, 1123 (1999).
17
Odendahl M., et al., J. Immunol. 165, 5970 (2000).
18
These observations may explain why a correlation between serum antibodies and antigen-binding memory B cells was not detected in a previous study where recently boosted individuals were analyzed (30).
19
Morell A., Terry W. D., Waldmann T. A., J. Clin. Invest. 49, 673 (1970).
20
Uhr J. W., Moller G., Adv. Immunol. 8, 81 (1968).
21
Manz R. A., Radbruch A., Eur. J. Immunol. 32, 923 (2002).
22
Celada F., J. Exp. Med. 125, 199 (1967).
23
Fearon D. T., Manders P., Wagner S. D., Science 293, 248 (2001).
24
Fagarasan S., Honjo T., Science 290, 89 (2000).
25
Macpherson A. J., et al., Science 288, 2222 (2000).
26
Martin F., Kearney J. F., Nature Rev. Immunol. 2, 323 (2002).
27
Kuppers R., Klein U., Hansmann M. L., Rajewsky K., N. Engl. J. Med. 341, 1520 (1999).
28
Paramithiotis E., Cooper M. D., Proc. Natl. Acad. Sci. U.S.A. 94, 208 (1997).
29
O'Connor B. P., Cascalho M., Noelle R. J., J. Exp. Med. 195, 737 (2002).
30
Leyendeckers H., et al., Eur. J. Immunol. 29, 1406 (1999).
31
We thank J. C. Howard, K. Karjalainen, G. Natoli, and F. Sallusto for critical reading of the manuscript. A.L. is supported by the Helmut Horten Foundation and by the Swiss National Science Foundation (grant 31-63885).
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Science
Volume 298 | Issue 5601
13 December 2002
13 December 2002
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Received: 12 July 2002
Accepted: 7 October 2002
Published in print: 13 December 2002
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