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.

Immuno-engineered organoids for regulating the kinetics of B-cell development and antibody production

“…Immune organoids may aid in further mechanistic studies of B-cell differentiation and organization, as discussed elsewhere 24,72 . For example, pre-B cells express the CD83 surface marker once they express a functional B-cell receptor (BCR).…”

“…For example, pre-B cells express the CD83 surface marker once they express a functional B-cell receptor (BCR). Although naive B cells express only low levels of CD83, activated B cells (both in vitro and in vivo) rapidly upregulate CD83 expression levels 72 . Yet there are several outstanding questions in the field of immunology and hematological malignancies because the function of CD83 during GC responses is not entirely clear 24,72 .…”

“…Although naive B cells express only low levels of CD83, activated B cells (both in vitro and in vivo) rapidly upregulate CD83 expression levels 72 . Yet there are several outstanding questions in the field of immunology and hematological malignancies because the function of CD83 during GC responses is not entirely clear 24,72 . We provide previously unpublished data that indicate that 3D immune organoids can induce a significant increase in CD83 expression in CD19 + B cells as compared with 2D cocultures on day 4 of differentiation, which corresponds to an ~35-fold increase over naive B cells on day 0 (P < 0.05; Supplementary Fig.…”

Thymic CD4 T cell selection requires attenuation of March8-mediated MHCII turnover in cortical epithelial cells through CD83

“…March1 −/− (Matsuki et al, 2007) and I-Aβ-K225R-EGFP mice have been described previously (McGehee et al, 2011). To generate the Cd83 −/− strain, mice carrying a floxed Cd83 allele (Krzyzak et al, 2016) were mated to germline-deleting E2a-Cre mice. March8 −/− mice were generated as described in Fig.…”

ATVB Distinguished Scientist Award

“…DC in human atherosclerotic lesions express CD83 and the content of CD83 + mature DC increased significantly in unstable plaques as compared to stable ones. 70, 71 CD83 regulates B cell activation and germinal center responses 72 as well as CD4 + T cell development. 73, 74 Although largely expressed by activated APCs, the costimulatory function of CD83 seems to be dispensable for murine T cell activation whilst CD83-stimulated human monocytes suppressed T cell responses.…”