Toll-like receptor mediated inflammation directs B cells towards protective antiviral extrafollicular responses.
Nat Commun
; 14(1): 3979, 2023 07 05.
Article
em En
| MEDLINE
| ID: mdl-37407556
ABSTRACT
Extrafollicular plasmablast responses (EFRs) are considered to generate antibodies of low affinity that offer little protection from infections. Paradoxically, high avidity antigen-B cell receptor engagement is thought to be the main driver of B cell differentiation, whether in EFRs or slower-developing germinal centers (GCs). Here we show that influenza infection rapidly induces EFRs, generating protective antibodies via Toll-like receptor (TLR)-mediated mechanisms that are both B cell intrinsic and extrinsic. B cell-intrinsic TLR signals support antigen-stimulated B cell survival, clonal expansion, and the differentiation of B cells via induction of IRF4, the master regulator of B cell differentiation, through activation of NF-kB c-Rel. Provision of sustained TLR4 stimulation after immunization shifts the fate of virus-specific B cells towards EFRs instead of GCs, prompting rapid antibody production and improving their protective capacity over antigen/alum administration alone. Thus, inflammatory signals act as B cell fate-determinants for the rapid generation of protective antiviral extrafollicular responses.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Plasmócitos
/
Linfócitos B
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article