JCSMR School Seminar Series - Siglecs on B cells and pDCs: inhibiting signaling and preventing autoimmunity

Professor Lars Nitschke, PhD,  Division of Genetics, Department of Biology, University of Erlangen, Germany

The Nitschke group works on Siglec proteins, which are inhibiting receptors on immune cells that can bind sialic acids as their ligands. We are especially interested in the functions of the B cell siglecs CD22 (Siglec-2) and Siglec-G, which we study with genetic mouse models. KO mice for both Siglecs show increased B-cell receptor (BCR)- induced signalling. While the deficiency of CD22 affects more conventional B cells, Siglec-G-deficiency affects a B cell subpopulation, the B-1 cells, which show increased Ca2+ signalling and a large expansion of their population, upon loss of Siglec-G. We study with mouse models how Siglec ligand binding affects the inhibitory signalling and find for both Siglecs, that ligand binding determines the association to the BCR and thereby controls the inhibitory signalling. Loss of CD22 or Siglec-G leads to spontaneous development of autoimmune disease in ageing mice. Siglec-H is another Siglec protein which is expressed exclusively on plasmacytoid dendritic cells and inhibits production of type I interferon (IFN-I) from this cell type. When infected with murine cytomegalovirus (MCMV), Siglec-H deficient mice develop a strong lupus-like autoimmune disease several weeks after infection, due to an ongoing and uncontrolled IFN-I production. This established an interesting link of a virus infection and induction of autoimmune disease, which is relevant also for human patients.

Lars Nitschke is a scientist working in the field of B cell immunology with a major research focus on the regulation of B cell immunity, B cell signalling and autoimmunity. His main research focus is on inhibitory receptors (Siglecs) on immune cells as regulators of lymphocyte activation. With newly generated genetic mouse models he studies the regulation of immune responses and the dysregulation of the immune system in autoimmune diseases.

Date & time

12–1pm 24 November 2017

Location

The Finkel Lecture Theatre, The John Curtin School of Medical Research, Building 131 Garran Road, ANU

Speakers

Host: Anselm Enders

Contacts

 Doris Morales
 +61 2 6125 4996

Updated:  19 November 2017/Responsible Officer:  Director, JCSMR/Page Contact:  Web Manager