Mechanisms of a novel regulatory B cell subset

Versiti Wisconsin, Inc., Milwaukee WI

Investigators

Linked publications & trials

Abstract

? DESCRIPTION (provided by applicant): Inflammation that accompanies chronic disease if uncontrolled leads to severe tissue damage and even death. B cells have emerged as an important attenuator of inflammation in a variety of diseases including autoimmunity and hypersensitivities. We were the first to show that B cells attenuated disease severity in autoimmunity. This was accomplished using the mouse model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE), where we demonstrated that mice with a deficiency in B cells due to genetic ablation (µMT) were unable to undergo spontaneous recovery. Shortly thereafter, the concept of regulatory B cells or Breg emerged. Subsequently, we discovered a regulatory loop between Breg and CD4+Foxp3+ T regulatory (Treg) cells whereby B cells promote the proliferation of Treg, which are essential for controlling the severity of inflammatory diseases. Of importance, we observed similar results in animal models of contact hypersensitivity and inflammatory bowel disease demonstrating therapeutic potential for Breg for the treatment of chronic inflammatory diseases. In subsequent experiments, we identified a unique Breg phenotype that we will use to uncover the mechanisms whereby Breg impact Treg proliferation, activation and function in inflammatory disease models. In addition, we will determine Breg localization and antigen experience. Finally, we will test the hypothesis that efficacy of B cell depletion by rituximab in MS is due to its inability to deplete Breg.