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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Peripheral blood-derived bovine dendritic cells promote IgG1-restricted B cell responses in vitro
Anna A Bajer1, David Garcia-Tapia, Kimberly R Jordan
1Department of Veterinary Pathobiology, Program for Prevention of Animal Infectious Diseases, University of Missouri, Columbia, MO 65211, USA.
Insights
Bovine dendritic cells (DCs) directly influence B cell responses by producing type 2 cytokines and expressing CD40L. This suggests a T cell-independent pathway for regulating humoral immunity and immunoglobulin production.
Area of Science:
- Immunology
- Cell Biology
- Dendritic Cell Function
Background:
- Humoral immune responses require T and B cell interactions for T-dependent antigen responses.
- Dendritic cells (DCs) play a critical role in regulating immune responses.
- The specific function of bovine peripheral blood-derived DCs (PB-DCs) in B cell regulation is not fully understood.
Purpose of the Study:
- To characterize bovine PB-DCs and their functional similarities to human interstitial DCs.
- To investigate the role of bovine PB-DCs in B cell activation and differentiation.
- To explore the potential for T cell-independent regulation of humoral responses by DCs.
Main Methods:
- Phenotypic analysis of bovine PB-DCs using flow cytometry for costimulatory molecules, MHC class II, CD14, and CD11c expression.
- Assessment of cytokine production, specifically type 2 cytokines like interleukin (IL)-13 and IL-10.
- Evaluation of direct interactions between PB-DCs and B cells, including CD40L expression and effects on B cell activation and differentiation.
Main Results:
- Bovine PB-DCs exhibit characteristics of human interstitial DCs, including moderate-to-high costimulatory molecule expression.
- PB-DCs produce signature type 2 cytokines (IL-13, IL-10) and express CD40L.
- Direct B cell-DC interactions influence B cell activation and differentiation, promoting a type 2 response pattern.
Conclusions:
- Bovine PB-DCs possess a phenotype and function analogous to human interstitial DCs.
- Direct interactions between bovine B cells and DCs can drive type 2-biased humoral responses.
- These findings suggest a significant role for direct B cell-DC communication in T cell-independent regulation of immunoglobulin production.
Abstract:
Regulation of humoral responses involves multiple cell types including the requirements for cognate interactions between T and B cells to drive CD40-dependent responses to T-dependent antigens. A third cell type has also been shown to play an essential role, the dendritic cell (DC). We demonstrate that bovine peripheral blood-derived (PB)-DC are similar in function to features described for human interstitial DC including the production of signature type 2 cytokines [interleukin (IL)-13, IL-10]. PB-DC express moderate-to-high costimulatory molecule expression, and major histocompatibility complex class II is negative for CD14 expression and has low or no expression of CD11c. Consistent with the interstitial phenotype is the ability of PB-DC to influence B cell activation and differentiation via direct expression of CD40L and type 2 cytokines. Collectively, these results suggest that direct B cell-DC interactions may promote an immunoglobulin-isotype expression pattern consistent with type 2 responses, independent of direct T cell involvement.
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