Abstract

Joint Seminar: Immunology in Pathology series and Immunology and Medicine series

Area of Study: Structure and function of B lymphocyte cell surface molecules that regulate B cell function, activation and signal transduction.

Overview: The focus of our laboratory is the identification, structural characterization, and functional analysis of cell surface molecules that regulate B lymphocyte development and function. Cell surface molecules allow B cells to communicate with the extracellular environment by serving as transmembrane regulators, receptors for soluble factors, or by mediating cell–cell interactions. Our studies of B-cell–associated cell surface receptors, including CD19 , CD20, CD21 , CD22 and CD83 , are aimed at determining how these molecules function, what their ligands are, how they generate transmembrane signals and regulate B cell development, survival and activation. The role of CD83 in dendritic and B cell biology is also being examined.

These studies lay the foundation for investigating mechanisms of immune dysregulation and the pathogenesis of immune disorders, such as autoimmunity, neoplastic transformation, and immunodeficiency syndromes. We have expertise in cellular immunology, biochemistry, and molecular biology and are applying a wide range of techniques in determining the function of these molecules. Many of these studies depend on the use of transgenic mice which overexpress these regulatory molecules or the generation and analysis of knockout mice lacking these receptors. Current studies are focused on identifying the molecular and cellular mechanisms by which B cells regulate T cell function and autoimmunity, with a particular emphasis on a regulatory B cell subset we identified that controls immune and inflammatory responses. Current studies also focus on identifying the molecular and cellular mechanisms by which CD19 , CD20 and CD22 mAb immunotherapies are effective for treating B cell malignancies and autoimmunity.