Analysis of the role of the B cell inhibitory receptor Siglec-G in autoimmunity and infection models
Final Report Abstract
B cell responses are regulated by inhibitory receptors, which can control the threshold of B cell activation. Inhibitory receptors are thought to prevent over-activation of B cells, which could potentially lead to autoimmunity. Our group works on B cell inhibitory receptors of the Siglec (Sialic acid binding immunoglobulin-like lectin) family. Siglecs bind specifically sialic acids, carbohydrates which occur in different forms and are expressed as terminal sugars on glycoproteins on cellular surfaces. Inhibitory signalling by Siglecs is mediated via inhibitory signalling motifs in their intracellular tails, to which tyrosine phosphatases are recruited that can inhibit signalling responses. We have previously characterized a new B cell inhibitory receptor, Siglec-G. We found that Siglec-G is particularly high expressed in B1 cells, a subpopulation of B cells. On these B1 cells, Siglec-G acts as an inhibitory receptor controlling their expansion and inhibiting their signalling. In this project we addressed the question, whether the loss of the Siglecg gene in mice leads to higher susceptibility to spontaneous autoimmunity or induced arthritis. We could show in a collagen-induced arthritis model that Siglec-G-deficient mice developed a more severe and prolonged disease than control mice. We also compared the transcriptome of Siglecg-/- B1 cells to control B1 cells and found interesting changes in genes involved in intracellular signalling pathways and in cellular selection.
Publications
- (2010) Siglec-G regulates B1 cell survival and selection. J Immunol. 185:3277-3278
Jellusova J, Düber S, Gückel E, Binder CJ, Weiss S, Voll R, Nitschke L
