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

• Published in: The Journal of clinical investigation Vol. 131; no. 12; pp. 1 - 11
• Main Authors: Rana, Minakshi, La Bella, Andrea, Lederman, Rivka, Volpe, Bruce T, Sherry, Barbara, Diamond, Betty
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 15.06.2021
• Subjects: Adoptive transfer; Antibody response; Antigen-antibody complexes; Antigen-antibody reactions; Antigens; Apoptosis; Bacteria; Biomedical research; Cecum; Complications and side effects; Dendritic cells; Flow cytometry; Gene expression; Health aspects; Hospital costs; IKK2 protein; Immune response; Immune response (humoral); Immunization; Immunoglobulins; Immunological research; Infections; Intercellular adhesion molecule 1; Lymphocytes; Lymphocytes B; Lymphocytes T; Sepsis; Tumor necrosis factor receptors; Tumor necrosis factor-α; Vascular cell adhesion molecule 1; United States; Antigen; Infectious disease; Immunoglobulins; Immunology
• ISSN: 1558-8238; 0021-9738; 1558-8238
• DOI: 10.1172/JCI146776

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) have reduced NP-specific high-affinity class-switched Ig antibodies compared to sham control mice following immunization with the T-dependent Ag, NP-CGG. NP-specific germinal center (GC) B cells in CLP mice exhibited reduced TNFα and AID mRNA expression compared to sham 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 LTbR compared to sham mice. Adoptive transfer studies showed there was no B cell-intrinsic defect. In summary, our data suggest that the reduced Ag-specific antibody response in CLP mice is secondary to a disruption in FDC and GC B cell function.