Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation |
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| Affiliation: | 1. Tom Kepler is at the Santa Fe Institute, 1660 Old Pecos Trail, Santa Fe, NM 87501, USA and the Biomathematics Program, Campus Box 8203, North Carolina State University, Raleigh, NC 27695, USA;2. Alan S. Perelson is at the Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA;1. Department of Environmental Health, Rollins School of Public Health Emory University, Atlanta, GA 30322-3090, USA;2. Center for Neurodegenerative Disease, School of Medicine, Emory University Atlanta, GA 30322-3090, USA;1. College of Natural Sciences and Health Sciences, Department of Health and Medicine, Carroll University, Waukesha, WI 53186, United States;2. College of Natural Sciences and Health Sciences, Department of Physical Sciences, Carroll University, Waukesha, WI 53186, United States;3. Rush Copley Center for Reproductive Health, Aurora, IL 60504, United States;4. Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 5321, United States;5. Department of OB/GYN, Medical College of Wisconsin, United States;1. University of Cambridge, School of Clinical Medicine, Cambridge, CB2 0QQ, UK;2. Department of Pathology, Papworth Hospital, Papworth Everard, CB23 3RE, UK;3. Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, CB22 3AT, UK;4. Division of Surgery and Interventional Sciences, Faculty of Medical Sciences, University College London, London, NW3 2QG, UK;5. Centre for Transplantation, Department of Renal Medicine, University College London, London, NW3 2QG, UK;6. Institute of Immunity and Transplantation, University College London, London, NW3 2QG, UK;1. College of Life Science, Hunan Normal University, Changsha 410013, China;2. Shanghai Institute of Biological Products, Shanghai 200052, China;1. Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642, United States;2. David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642, United States;3. Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY 14642, United States |
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| Abstract: | Affinity maturation of the humoral immune response by somatic hypermutation is marked by a rapid and dramatic increase in affinity for the eliciting antigen. We suggest that the optimal mutation schedule is one in which periods of rapid mutation alternate with periods of mutation-free growth. The multicompartmental structure of the germinal center, together with re-entry of positively selected B cells back into the germinal center, will naturally implement such a schedule, thereby providing an anatomical basis for the efficiency of the germinal center reaction. |
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