Defining Tolerance Mechanisms Regulating TLR-Induced B-cell Autoimmunity in Human SLE



Amanda Wisz


Research Mentor:

Dr. Barb Vilen, PhD


Clinical Co-mentor:

Dr. Robert Roubey, MD

Home Department Microbiology and Immunology
Project Description Autoreactive B cells can be stimulated through the innate immune Toll-like Receptor (TLR) to secrete harmful self antibodies that lead to autoimmune disease, like Systemic Lupus Erythematosis (SLE). Our lab has identified two subsets of immune cells, macrophages and myeloid dendritic cells, as repressors of autoreactive B cells in mice. Macrophages and dendritic cells secrete soluble proteins that prevent autoreactive B cells from releasing autoantibodies after stimulation through TLR4. Humans, however, express low, if any, TLR4, but rely on two other receptors, TLR9 and TLR7. My project seeks to determine whether a similar mechanism of cell-mediated repression can control autoreactive B cells stimulated through TLR7 both in the mouse and the human patient. By studying a subset of naturally occurring autoreactive B cells in healthy controls, we can determine what mechanisms keep them anergic, allowing us to then identify some of the defects that allow the break of B cell tolerance seen in SLE.