Yufeng Peng, PhD

University of Washington, Seattle, WA

2012 B Cells

Yufeng Peng, PhDHow does apoptotic cell accumulation contribute to lupus?

The Study and What it Means for Patients

“Is a breakdown in the body’s housecleaning to blame for the lupus immune system’s self-attack? By revealing how dying cells not cleared effectively may trigger immune cells to attack those cells’ DNA and proteins, we could discover potential targets for interventions.”

Summary:
Cells that die as part of everyday tissue maintenance and repair are normally removed by the body’s housekeeping clearance systems. But if these systems break down and dying cells are not cleared effectively they can activate the immune system, inducing antibody responses to DNA and proteins contained in dying cells. Dr Peng will investigate how dying cells activate the immune system using a mouse model in which dying cells accumulate due to a defective clearance protein, MFG-E8.

Scientific abstract:
Many lupus specific antigens are exposed on the surface of apoptotic cells. Defective clearance of apoptotic cells has been linked to lupus in human and mice. In order to understand how accumulation of apoptotic cell leads to break down of B cell tolerance to self and chronic inflammation, we systematically examined the effects of delayed clearance of apoptotic cells in MFG-E8 KO mice. MFG-E8, a soluble milk protein, binds to phosphatidylserine on apoptotic cells and facilitates their removal through its interaction with ƒÑvƒÒ3 and ƒÑvƒÒ5 integrins on phagocytes. Despite the lack of typical lupus antibodies in MFG-E8-/- B6 mice, we found elevated levels of IgG2c binding activity to apoptotic cells in the serum and accumulation of IgG2c positive plasma cells associated with intensive C3 deposited on FDCs in the spleen. In addition to the B cell abnormalities, an altered hemokine/chemokine receptor profile associated with large clusters of dendrtiic cells was observed in spleen cells from MFG-E8-/- mice. In this proposal, we will investigate the signals required for apoptotic cell induced antibody response in MFG-E8-/- mice. The success of our investigation will provide much needed insight into the etiology of SLE and potential targets for future intervention.