TY - JOUR
T1 - Reconciling repertoire shift with affinity maturation
T2 - The role of deleterious mutations
AU - Shannon, Michele
AU - Mehr, Ramit
PY - 1999/4/1
Y1 - 1999/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033120054&partnerID=8YFLogxK
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C2 - 10201914
AN - SCOPUS:0033120054
SN - 0022-1767
VL - 162
SP - 3950
EP - 3956
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -