Abstracts (complete list) - Wissenschaft Online

Birte Kretschmer, Katja Lüthje, Andreas H. Guse, Svenja Ehrlich, Friedrich Koch-
Nolte, Friedrich Haag, Bernhard Fleischer, Minka Breloer
CD83 modulates B cell function in vivo and in vitro
The murine transmembrane glycoprotein CD83 is an important regulator of both:
thymic T cell maturation and peripheral T cell responses. Here we provide evidence that
CD83 is also involved in the regulation of B cell function. We therefore compared the
function of CD83Tg B cells that overexpress CD83 and CD83 mutant (CD83mu) B cells
that display a drastically reduced CD83 expression. Correlating with CD83 expression,
the basic as well as the LPS induced expression of the activation markers CD86 and
MHC-II was significantly increased on CD83Tg B cells and reciprocally decreased on
CD83mu B cells. Wild-type B cells rapidly upregulate CD83 within three hours post BCR
or TLR engagement. The forced premature expression of CD83 on CD83Tg B cells
resulted in reduced calcium signaling, reduced Ig secretion and a reciprocally increased
IL-10 production upon in vitro activation. This altered phenotype was mediated by CD83
expressed on the B cells themselves, since it was observed in purified B cells and
therefore in the absence of accessory cells. Although reduced CD83 expression on
CD83mu B cells did not alter the response of whole spleen cell cultures to LPS
stimulation in vitro, a slight reduction in IL-10 release together with a non-significant
increase in Ig secretion was observed in purified CD83mu B cells.
Employing a non-conditional transgenic model we cannot rule out the possibility that
artificial CD83 expression on B cells during their maturation within the CD83Tg mice
results in the generation of dysfunctional B cells. Nevertheless we were able to show
that the treatment of non-Tg C57BL/6 mice with anti-CD83 mAb led to a dose
dependent 10-fold increase in the antigen-specific IgG1 response to TI immunization
thus demonstrating a genuine role for naturally induced CD83 in the regulation of
peripheral B cell function. Although we still have to define the CD83-positive cell
population(s) targeted by the anti-CD83 mAb in vivo, this finding already demonstrates
a genuine role for naturally induced CD83 in the regulation of peripheral B cell function.