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Science 13 July 2001:
Vol. 293. no. 5528, pp. 248 - 250
DOI: 10.1126/science.1062589
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Arrested Differentiation, the Self-Renewing Memory Lymphocyte, and Vaccination

Douglas T. Fearon,1* Peter Manders,1 Simon D. Wagner12

Vaccination for persistent viral or bacterial infections must program the immune system for a lifelong need to generate antigen-specific effector lymphocytes. How the immune system does this is not known, but recent studies have shown that a subset of B lymphocytes, the germinal center B cell, is capable of self-renewal because it expresses a transcriptional repressor, BCL6, that blocks terminal differentiation. If a similar mechanism for arresting differentiation exists for long-lived, antigen-selected lymphocytes, a stem cell-like capacity for self-renewal could be the basis for the continual generation of effector lymphocytes from the memory pool. Understanding how to regulate the terminal differentiation of lymphocytes will improve immunotherapeutic approaches for chronic infectious diseases and cancer.

1 Wellcome Trust Immunology Unit, School of Clinical Medicine, University of Cambridge, MRC Centre, Cambridge CB2 2SP, UK.
2 Department of Haematology, Addenbrookes Hospital, Cambridge CB2 2SP, UK.
*   To whom correspondence should be addressed. E-mail: dtf1000{at}cus.cam.ac.uk

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