In this thesis the role of murine
FcgammaR in autoimmune diseases is analyzed with special focus on
arthritis and lupus. Series of studies performed with a variety of
arthritis models established in mice deficient for one or more FcgammaR
provided direct evidence for a prominent role of FcgammaR in arthritis
(Chapter 2). Chapters 3 to 5 provide new insights into the role of
individual FcgammaR in arthritis pathology. The precise contribution of
FcgammaRIIB to the development of autoimmunity has been a matter of
debate. In Chapter 6, we provide direct evidence that FcgammaRIIB on its
own plays a limited role in the development of spontaneous autoimmunity
in C57Bl/6 mice. Our results suggest that the role of FcgammaRIIB in
the development of spontaneous autoimmunity (Systemic Lupus
Erythematosus) is more restricted as originally postulated on the basis
of the phenotype of FcgammaRIIB129-/- mice, whereas
its role in induced autoimmunity is prominent, supporting the
hypothesis that FcgammaRIIB represents a late checkpoint in B cell
tolerance. In Chapter 7 we describe the generation and characterization
of a novel B cell-specific inducible Cre transgenic mouse line. The
results presented in this thesis provide new insights in the role of
FcgammaRs in protective immunity and immuno-pathology.LEI Universiteit LeidenReumafonds, JE Jurriaanse Stichting, Greiner Bio-OneTumorgenetic
