Abstract:
:The germinal centre reaction (GCR) is a fundamental component of the immune response to T-dependent antigens, during which the immunoglobulin (Ig) genes of B cells experience somatic hypermutation and selection. A maximum-likelihood method on DNA sequence data from 16 individual germinal centres was used to infer that the waiting time for position 33 key (high-affinity) mutations in the anti-(4-hydroxy-3-nitrophenyl) acetyl (NP) response is 8.3 days. This is in marked contrast to the prediction of a key mutant each generation (waiting time about 1/3 day) obtained from a simple model and parameters available in the literature. This disagreement is resolved in part by the finding that the targeted base occurs in a cold spot for hypermutation, raising the predicted waiting time to 2.3 days, although this value remains significantly lower than that inferred from the sequence data. It is proposed that the remaining disparity is attributable to some further stochastic process in the GCR: many early key mutations arise but fail to 'take root' within the GC, either due to emigration or failure of cognate T cell/B cell interaction. Furthermore, it is argued that the frequency with which position 33 mutations are found in secondary responses to NP indicates the presence of selection after the GCR.
journal_name
Immunol Cell Bioljournal_title
Immunology and cell biologyauthors
Radmacher MD,Kelsoe G,Kepler TBdoi
10.1046/j.1440-1711.1998.00753.xsubject
Has Abstractpub_date
1998-08-01 00:00:00pages
373-81issue
4eissn
0818-9641issn
1440-1711journal_volume
76pub_type
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