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The Journal of Immunology, 1999, 162: 3950-3956.
Copyright © 1999 by The American Association of Immunologists

Reconciling Repertoire Shift with Affinity Maturation: The Role of Deleterious Mutations1

Michele Shannon and Ramit Mehr2

Department of Molecular Biology, Princeton University, Princeton, NJ 08544

The shift in Ab repertoire, from Abs dominating certain primary B cell responses to genetically unrelated Abs dominating subsequent "memory" responses, challenges the accepted paradigm of affinity maturation. We used mathematical modeling and computer simulations of the dynamics of B cell responses, hypermutation, selection, and memory cell formation to test hypotheses attempting to explain repertoire shift. We show that repertoire shift can be explained within the framework of the affinity maturation paradigm, only when we recognize the destructive nature of hypermutation: B cells with a high initial affinity for the Ag are less likely to improve through random mutations.




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