Reconciling repertoire shift with affinity maturation: The role of deleterious mutations

Michele Shannon, Ramit Mehr

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3950-3956
Number of pages7
JournalJournal of Immunology
Volume162
Issue number7
StatePublished - 1 Apr 1999
Externally publishedYes

Funding

FundersFunder number
National Institute of General Medical SciencesR37GM020964

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