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Follicular dendritic cell dysfunction contributes to impaired antigen-specific humoral responses in sepsis-surviving mice.

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 LTβR 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.

PROVIDER: S-EPMC8203464 | BioStudies |

REPOSITORIES: biostudies

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