CD83 Modulates B Cell Activation and Germinal Center Responses.

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.

• Authors: Lena Krzyzak, Christine Seitz, Anne Urbat, Stefan Hutzler, Christian Ostalecki, Joachim Gläsner, Andreas Hiergeist, André Gessner, Thomas H Winkler, Alexander Steinkasserer, Lars Nitschke
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 196 Issue 9 Pg. 3581-94 (05 01 2016) ISSN: 1550-6606 [Electronic] United States
• PMID: 26983787 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 by The American Association of Immunologists, Inc.

Chemical References

• Antigens, CD
• B7-2 Antigen
• CD83 antigen
• Cd86 protein, mouse
• Immunoglobulin G
• Immunoglobulins
• Membrane Glycoproteins
• Immunoglobulin E

Topics

• Animals
• Antigens, CD (genetics, immunology)
• B-Lymphocytes (immunology, physiology)
• B7-2 Antigen (genetics, immunology)
• Borrelia burgdorferi (immunology)
• Dendritic Cells (immunology)
• Genes, MHC Class II (genetics, immunology)
• Germinal Center (cytology, immunology)
• Immunoglobulin E (blood, immunology)
• Immunoglobulin G (blood, immunology)
• Immunoglobulins (deficiency, genetics, immunology)
• Lymphocyte Activation
• Membrane Glycoproteins (deficiency, genetics, immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• T-Lymphocytes (immunology)
• Th2 Cells (immunology)