Abstract:
:Activation-induced deaminase (AID) is the master regulator of class switch recombination (CSR) and somatic hypermutation (SHM), but the mechanisms regulating AID function are obscure. The differential pattern of switch plasmid activity in three IgM(+)/AID(+) and two IgG(+)/AID(+) B cell lines prompted an analysis of global gene expression to discover the origin of these cells. Gene profiling suggested that the IgG(+)/AID(+) B cell lines derived from germinal center B cells. Analysis of SHM potential demonstrates that the IgVkappa domains are inducibly diversified at high rate during in vitro culture. The mutation spectra focused to A:T base pairs, revealing a component of the hypermutation program that occurs preferentially during phase 2 of SHM. The A:T error spectra were analyzed and were not characteristic of polymerase eta activity. A differential pattern of three consensus motifs used for A:T base substitutions was observed in WT and Poleta-, Msh2- and Msh6-deficient B cells. Strikingly, mutations in our B cell lines recapitulated the mutable motif profile for Poleta and Msh2 deficiency, respectively, and suggest that an additional pathway for the generation of A:T mutations in SHM is conserved in mouse and human.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Bhattacharya P,Grigera F,Rogozin IB,McCarty T,Morse HC 3rd,Kenter ALdoi
10.1002/eji.200737664subject
Has Abstractpub_date
2008-01-01 00:00:00pages
227-39issue
1eissn
0014-2980issn
1521-4141journal_volume
38pub_type
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journal_title:European journal of immunology
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journal_title:European journal of immunology
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