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CD83 Modulates B Cell Activation and Germinal Center Responses
Lena Krzyzak1, Christine Seitz1, Anne Urbat2
1Department of Immune Modulation, University Hospital Erlangen, 91052 Erlangen, Germany;
Insights
CD83 is crucial for B cell activation and germinal center (GC) responses. Its absence impairs B cell proliferation, alters GC composition, and enhances IgE antibody production, impacting immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD83 is a dendritic cell maturation marker.
- CD83 expression in B cells, particularly during germinal center (GC) reactions, suggests a role in B cell immunity.
- Previous studies using CD83 knockout mice were confounded by T cell deficiencies.
Purpose of the Study:
- To investigate the specific function of CD83 in B cell activation and GC responses.
- To overcome limitations of global CD83 knockout models by creating a B cell-specific conditional knockout.
Main Methods:
- Generation of a B cell-specific CD83 conditional knockout (CD83 B-cKO) mouse model.
- Analysis of B cell activation, proliferation, and MHC class II/CD86 expression in vitro.
- Assessment of GC responses post-immunization and during Borrelia burgdorferi infection.
- Competitive repopulation assays using mixed bone marrow chimeras.
Main Results:
- CD83 B-cKO B cells exhibited impaired proliferation and defective upregulation of MHC class II and CD86.
- GC analysis revealed a shift in B cell populations, with increased dark zone B cells in CD83 B-cKO mice.
- No significant changes in IgG levels or affinity maturation were observed, but IgE responses were enhanced.
- CD83-deficient B cells showed a competitive disadvantage in GC responses.
- CD83 B-cKO mice displayed defective bacterial clearance and a Th2-skewed response with elevated IgE.
Conclusions:
- CD83 plays a significant role in B cell activation and proliferation.
- CD83 influences the composition of GC B cell populations.
- CD83 modulates IgE antibody production and overall immune response dynamics in vivo.
Abstract:
CD83 is a maturation marker for dendritic cells. In the B cell lineage, CD83 is expressed especially on activated B cells and on light zone B cells during the germinal center (GC) reaction. The function of CD83 during GC responses is unclear. CD83(-/-) mice have a strong reduction of CD4(+) T cells, which makes it difficult to analyze a functional role of CD83 on B cells during GC responses. Therefore, in the present study we generated a B cell-specific CD83 conditional knockout (CD83 B-cKO) model. CD83 B-cKO B cells show defective upregulation of MHC class II and CD86 expression and impaired proliferation after different stimuli. Analyses of GC responses after immunization with various Ags revealed a characteristic shift in dark zone and light zone B cell numbers, with an increase of B cells in the dark zone of CD83 B-cKO mice. This effect was not accompanied by alterations in the level of IgG immune responses or by major differences in affinity maturation. However, an enhanced IgE response was observed in CD83 B-cKO mice. Additionally, we observed a strong competitive disadvantage of CD83-cKO B cells in GC responses in mixed bone marrow chimeras. Furthermore, infection of mice with Borrelia burgdorferi revealed a defect in bacterial clearance of CD83 B-cKO mice with a shift toward a Th2 response, indicated by a strong increase in IgE titers. Taken together, our results show that CD83 is important for B cell activation and modulates GC composition and IgE Ab responses in vivo.
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