Engagement of CD83 on B cells modulates B cell function in vivo.

TY - JOUR

T1 - Engagement of CD83 on B cells modulates B cell function in vivo.

AU - Kretschmer, Birte

AU - Lüthje, Katja

AU - Schneider, Stefanie

AU - Fleischer, Bernhard

AU - Breloer, Minka

PY - 2009

Y1 - 2009

N2 - 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 up-regulated 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.

AB - 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 up-regulated 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 182

SP - 2827

EP - 2834

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 5

M1 - 5

ER -