The Role of Dendritic Cells and Macrophages in Regulating BCR Activation and Adaptive Immune Responses



Shannon Jones


Research Mentor:

Dr. Barb Vilen, PhD


Clinical Co-Mentor;

Dr. Robert Roubey, MD

Project Description:

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease that results from a widespread loss of immune tolerance to nuclear self-antigens. Because SLE is characterized by the production of autoantibodies to nuclear components, it is clear the hyperactive, autoreactive B cells play a central role in the pathogenesis of this disease.  In order to develop more effective treatments, and to possibly restore tolerance, it is necessary to understand the mechanisms that normally regulate autoreactive B cells and how these become dysregulated in autoimmune disease.

Our lab recently described a novel mechanism of tolerance in which dendritic cells (DCs) and macrophages (MFs) selectively repress autoreactive B cells during innate immune responses. We now propose that DCs and MFs can also regulate B cells during adaptive immune responses through the modulation of B Cell Receptor (BCR) activation. We hypothesize that DCs and MFs are a major regulator of both naïve and autoreactive BCR-induced B cell activity, and that DCs and MFs preferentially regulate autoreactive B cells through co-localization.

My project focuses on defining the role of DCs and MFs in the regulation of BCR activation and subsequent B cell function.   Future directions include determining whether this mechanism of tolerance is defective in lupus-prone mice, and to eventually determine whether this mechanism is also defective in SLE patients.