Generation of functional murine CD11c+ age-associated B cells in the absence of B cell T-bet expression.
Eur J Immunol
; 49(1): 170-178, 2019 01.
Article
em En
| MEDLINE
| ID: mdl-30353919
ABSTRACT
Age-associated B cells (ABC), a novel subset of activated B cells defined by CD11b and CD11c expression, have been linked with both protective anti-viral responses and the pathogenesis of systemic autoimmunity. Expression of the TH 1 lineage transcription factor T-bet has been identified as a defining feature of ABC biology, with B cell-intrinsic expression of this transcription factor proposed to be required for ABC formation. In contrast to this model, we report that Tbx21 (encoding T-bet)-deficient B cells upregulate CD11b and CD11c surface expression in vitro in response to integrated TLR and cytokine signals. Moreover, B cell-intrinsic T-bet deletion in a murine lupus model exerted no impact of ABC generation in vivo, with Tbx21-/- ABCs exhibiting an identical surface phenotype to wild-type (WT) ABCs. Importantly, WT and Tbx21-/- ABCs sorted from autoimmune mice produced equivalent amounts of IgM and IgG ex vivo following TLR stimulation, indicating that T-bet-deficient ABCs are likely functional in vivo. In summary, our data contradict the established literature by demonstrating that T-bet expression is not uniformly required for ABC generation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Nefrite Lúpica
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Envelhecimento
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Linfócitos B
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Proteínas com Domínio T
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Lúpus Eritematoso Sistêmico
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos