Mechanisms of B Cell Responses in Autoimmune Disease: C12-ALE05-CSF

Sponsor: Duke University

Location(s): United States


This work is conducted in collaboration with the Autoimmunity Center of Excellence (ACE) at Duke. Tedder and colleagues have found that a phenotypically unqiue subset of B cells secreting IL-10 (called B10 cells) serve as critical negative regulators during adaptive CD4+ T cells Responses, and dramatically suppress Th1 immune Responses and Autoimmune Disease in mice. For Basic Research Project 1, they will examine the hypothesis that antigen-specific regulatory B10 cells modulate Autoimmune Responses in mice and man and that they can be manipulated for therapeutic gain. A picture is gradually emerging about the precursors of self-reactive B cells in Autoimmune Disease. Kelsoe and coworkers in Basic Research Project 2 will investigate developmentally regulated expression of activated cytidine deaminase (AID) in human fetal and neonatal pre-, pro, and immature/transitional B cells and its relationship to the generation of self-reactive B cells in human Autoimmune Disease, potentially eludidating another pathway of B Cell self-reactivity outside the confines of normal tolerance Mechanisms. Two new clinical trials to investigate lymphotoxin-beta receptor fusion protein as a treatment for primary Sj"gren's syndrome, and rituximab therapy for bullous pemphigoid. A Pilot Research Project will engineer tetramers of self-antigen enabling the identification and characterization of self-reactive B cells, which will have implications for the goals of the clinical and other basic research projects. Overall, the Duke ACE will bridge these basic and clinical studies to advance our understanding of Autoimmune Disease. The B Cell is a type of immune Cell essential to autoimmunity. The goal of the proposed Autoimmunity Center of Excellence at Duke is to improve our understanding of the roles played by B cells in human Autoimmune Disease. The projects are designed to be highly integrative between the bench and the bedside, with collaborations between basic and clinical scientists. These studies may lead to better treatments.