Activation-Induced Cytidine Deaminase Expression in Human B Cell Precursors Is Essential for Central B Cell Tolerance.
Immunity
; 43(5): 884-95, 2015 Nov 17.
Article
em En
| MEDLINE
| ID: mdl-26546282
ABSTRACT
Activation-induced cytidine deaminase (AID), the enzyme-mediating class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes, is essential for the removal of developing autoreactive B cells. How AID mediates central B cell tolerance remains unknown. We report that AID enzymes were produced in a discrete population of immature B cells that expressed recombination-activating gene 2 (RAG2), suggesting that they undergo secondary recombination to edit autoreactive antibodies. However, most AID+ immature B cells lacked anti-apoptotic MCL-1 and were deleted by apoptosis. AID inhibition using lentiviral-encoded short hairpin (sh)RNA in B cells developing in humanized mice resulted in a failure to remove autoreactive clones. Hence, B cell intrinsic AID expression mediates central B cell tolerance potentially through its RAG-coupled genotoxic activity in self-reactive immature B cells.
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Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
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Citidina Desaminase
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Células Precursoras de Linfócitos B
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Tolerância Central
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos