Bach2 regulates AID-mediated immunoglobulin gene conversion and somatic hypermutation in DT40 B cells.
Eur J Immunol
; 47(6): 993-1001, 2017 06.
Article
em En
| MEDLINE
| ID: mdl-28301039
The transcription factor Bach2 is required for germinal center formation, somatic hypermutation (SHM), and class-switch recombination (CSR) of immunoglobulins. SHM and CSR are initiated by activation-induced cytidine deaminase (AID) which has potential to induce human B cell lymphoma. To understand the role of Bach2 in AID-mediated immunoglobulin gene diversification processes, we established a BACH2-deficient DT40 B cell line. We show that in addition to allowing SHM, Bach2 drives immunoglobulin gene conversion (GCV), another AID-dependent antibody gene diversification process. We demonstrate that Bach2 promotes GCV by increasing the expression of AID. Importantly, we found that the regulation of AID is independent of Blimp-1 and that BACH2-deficient cells have altered expression of several genes regulating AID expression, stability and function. Furthermore, re-expression of BACH2 or AID in Bach2KO cells restored the SHM and GCV defects. These results demonstrate that Bach2 has a previously unappreciated role in the production of high-affinity antibodies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
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Genes de Imunoglobulinas
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Linfócitos B
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Citidina Desaminase
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Hipermutação Somática de Imunoglobulina
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Fatores de Transcrição de Zíper de Leucina Básica
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Conversão Gênica
Limite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Finlândia