Autoreactive B cells in SLE, villains or innocent bystanders?
Immunol Rev
; 292(1): 120-138, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31631359
ABSTRACT
The current concepts for development of autoreactive B cells in SLE (systemic lupus erythematosus) focus on extrinsic stimuli and factors that provoke B cells into tolerance loss. Traditionally, major tolerance loss pathways are thought to be regulated by factors outside the B cell including autoantigen engagement of the B-cell receptor (BCR) with simultaneous type I interferon (IFN) produced by dendritic cells, especially plasmacytoid dendritic cells (pDCs). Later, in autoreactive follicles, B-cells encounter T-follicular helper cells (Tfh) that produce interleukin (IL)-21, IL-4 and pathogenic cytokines, IL-17 and IFN gamma (IFNÉ£). This review discusses these mechanisms and also highlights recent advances pointing to the peripheral transitional B-cell stage as a major juncture where transient autocrine IFNß expression by developing B-cells imprints a heightened susceptibility to external factors favoring differentiation into autoantibody-producing plasmablasts. Recent studies highlight transitional B-cell heterogeneity as a determinant of intrinsic resistance or susceptibility to tolerance loss through the shaping of B-cell responsiveness to cytokines and other environment factors.
Palavras-chave
BXD2; IFNß; IL-17; IL-21; SLE; autoantibodies; autoimmunity; follicular T-helper cells; germinal center B cells; lupus; lymphotoxin beta; marginal zone macrophages; marginal zone-precursor B cells; plasmacytoid dendritic cells; regulator of G-protein signaling; transitional stage 1 B cells; type I IFNs
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
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Linfócitos B
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Autoimunidade
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Tolerância Imunológica
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Lúpus Eritematoso Sistêmico
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Immunol Rev
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos