Follicular dendritic cell dysfunction contributes to impaired antigen-specific humoral responses in sepsis-surviving mice.
J Clin Invest
; 131(12)2021 06 15.
Article
en En
| MEDLINE
| ID: mdl-33956665
ABSTRACT
Sepsis survivors exhibit impaired responsiveness to antigen (Ag) challenge associated with increased mortality from infection. The contribution of follicular dendritic cells (FDCs) in the impaired humoral response in sepsis-surviving mice is investigated in this study. We demonstrated that mice subjected to sepsis from cecal ligation and puncture (CLP mice) have reduced NP-specific high-affinity class-switched Ig antibodies (Abs) compared with sham-operated control mice following immunization with the T cell-dependent Ag, NP-CGG. NP-specific germinal center (GC) B cells in CLP mice exhibited reduced TNF-α and AID mRNA expression compared with sham-operated mice. CLP mice showed a reduction in FDC clusters, a reduced binding of immune complexes on FDCs, and reduced mRNA expression of CR2, ICAM-1, VCAM-1, FcγRIIB, TNFR1, IKK2, and LTßR compared with sham-operated mice. Adoptive transfer studies showed that there was no B cell-intrinsic defect. In summary, our data suggest that the reduced Ag-specific Ab response in CLP mice is secondary to a disruption in FDC and GC B cell function.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Sepsis
/
Células Dendríticas Foliculares
/
Inmunidad Humoral
Límite:
Animals
Idioma:
En
Revista:
J Clin Invest
Año:
2021
Tipo del documento:
Article