Engagement of CD83 on B Cells Modulates B Cell Function In Vivo

Abstract

The transmembrane glycoprotein CD83 is an important regulator of both thymic T cell maturation and peripheral T cell response. Recent studies suggested that CD83 is also involved in the regulation of B cell maturation, activation, and homeostasis. In this study, we show that in vivo overexpression of CD83 dose dependently interfered with the Ig response to thymus-dependent and thymus-independent model Ag immunization. CD83 deficiency, in contrast, which was restricted to B cells in mixed bone marrow chimeras, led to unchanged or even slightly increased Ig responses. Strikingly, the engagement of CD83 that is naturally upregulated on wild-type B cells by injection of anti-CD83 mAb in vivo induced a 100-fold increase in the IgG1 response to immunization. Kinetic analysis revealed that CD83 had to be engaged simultaneously or shortly after the B cell activation through injection of Ag, to modulate the IgG1 secretion. Furthermore, using mixed bone marrow chimeras in which either selectively the B cells or the dendritic cells were CD83 deficient, we demonstrate that anti-CD83 mAb mediated its biologic effect by engaging CD83 on B cells and not on CD11c ؉ dendritic cells. Taken together, we provide strong evidence that CD83 transduces regulatory signals into the very B cell on which it is expressed.

CD83 Modulates B Cell Activation and Germinal Center Responses

“…The reduced Ig response in total CD83 KO animals can be explained by a strong reduction of CD4 + Th cells, which normally trigger Ig class switch in T cell-dependent immune responses. This is in accordance with findings from bone marrow chimeras using transfer of total CD83 KO bone marrow in WT animals, which show no influence on the humoral responses (13). In contrast, overexpression of CD83 in CD83tg mice led to reduced humoral responses to thymus-dependent and thymus-independent Ags (13).…”

“…2/2 bone marrow were performed (13). Expression of CD83 on germinal center (GC) lymphocytes was first shown in 1992 (1), and since 2012 it has been used as a marker for light zone (LZ) B cells during GC reactions (14).…”

CD11c Controls Herpes Simplex Virus 1 Responses To Limit Virus Replication during Primary Infection

“…The possibility of such immune modulation is unknown; however, the differential stimulation requirements of CD11c-positive and CD11c-negative DCs have already been elucidated (28). Modulation of CD83 may also be a potential target, as increased CD83 has been correlated with an increased antibody response in B cells (29) and increased expression of MHC class II and CD86 costimulatory molecules on DCs (60). Similar to our results, the engagement of the CD83 ligand (CD83L) preferentially enriches and significantly amplifies the number of antigenspecific CD8…”

Topical Application of Soluble CD83 Induces IDO-Mediated Immune Modulation, Increases Foxp3+ T Cells, and Prolongs Allogeneic Corneal Graft Survival

“…We and others reported that recombinant sCD83 inhibits DC maturation (28,29) and blocks T cell stimulation (28,30). It has also been reported that CD83 is a regulator of B cell function (31,32).…”