Ikaros Is a Negative Regulator of B1 Cell Development and Function.
J Biol Chem
; 291(17): 9073-86, 2016 Apr 22.
Article
em En
| MEDLINE
| ID: mdl-26841869
ABSTRACT
B1 B cells secrete most of the circulating natural antibodies and are considered key effector cells of the innate immune response. However, B1 cell-associated antibodies often cross-react with self-antigens, which leads to autoimmunity, and B1 cells have been implicated in cancer. How B1 cell activity is regulated remains unclear. We show that the Ikaros transcription factor is a major negative regulator of B1 cell development and function. Using conditional knock-out mouse models to delete Ikaros at different locations, we show that Ikaros-deficient mice exhibit specific and significant increases in splenic and bone marrow B1 cell numbers, and that the B1 progenitor cell pool is increased â¼10-fold in the bone marrow. Ikaros-null B1 cells resemble WT B1 cells at the molecular and cellular levels, but show a down-regulation of signaling components important for inhibiting proliferation and immunoglobulin production. Ikaros-null B1 cells hyper-react to TLR4 stimulation and secrete high amounts of IgM autoantibodies. These results indicate that Ikaros is required to limit B1 cell homeostasis in the adult.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
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Imunoglobulina M
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Células da Medula Óssea
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Subpopulações de Linfócitos B
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Fator de Transcrição Ikaros
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Células Precursoras de Linfócitos B
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
França