Efficient Induction of Ig Gene Hypermutation in Ex Vivo-Activated Primary B Cells.
J Immunol
; 199(9): 3023-3030, 2017 11 01.
Article
em En
| MEDLINE
| ID: mdl-28939756
ABSTRACT
Activation-induced cytidine deaminase (AID) initiates both somatic hypermutation (SHM) and class switch recombination (CSR) of Ig genes. How AID is targeted to the Ig V gene and switch region to trigger SHM and CSR remains elusive. Primary B cells stimulated with CD40L plus IL-4 or LPS plus IL-4 undergo efficient CSR, but it has been difficult to induce SHM in these cells. In the current study, we used B cells from B1-8hi mice carrying a prerecombined VH186.2DFL16.1JH2 Ab gene to investigate the induction of SHM under in vitro culture conditions. B1-8hi splenic B cells stimulated with CD40L plus IL-4 or LPS plus IL-4 underwent robust CSR to IgG1, but failed to generate SHM in the VH186.2 gene. Remarkably, ectopic expression of AID in AID-deficient, but not wild-type, B1-8hi B cells induced efficient SHM at a rate close to that observed in germinal center B cells. We further established an AID-deficient CH12 B lymphoma line and found that ectopic expression of AID in the mutant line, but not in AID-sufficient CH12 cells, induced efficient point mutations and deletions in the V gene. These results demonstrate that the endogenous AID in ex vivo-activated primary B and B lymphoma cells not only cannot induce SHM but also inhibit the induction of SHM by the exogenous AID. Our results further suggest that the spatiotemporal distribution and/or posttranslational modification of AID strongly affects the induction of SHM in ex vivo-activated primary B cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina G
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Linfócitos B
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Ativação Linfocitária
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Citidina Desaminase
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Hipermutação Somática de Imunoglobulina
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
China