Our laboratory is interested in understanding how B lymphocytes are regulated to produce antibodies.
We are particularly interested in determining how antibody responses to carbohydrate antigens are controlled. Antibody responses to carbohydrate antigens are important for many aspects of human health and disease
While carbohydrate-based vaccines have long been limited to polysaccharides isolated from pathogenic encapsulated extracellular bacteria, there is currently intense interest in developing carbohydrate-based vaccines for inducing antibodies directed at additional types of bacteria, parasites, fungi, viruses, and even aberrantly glycosylated tumor cells.
Regulation of B Cell Responses
We are currently assessing regulation of B cell responses to diverse carbohydrate antigens and the protective nature of anti-carbohydrate antibodies in several clinically relevant diseases, including Streptococcus pneumoniae and Klebsiella pneumoniae infections and cancer.
Anti-carbohydrate antibody responses are regulated in a manner that is distinct from proteins which behave as T cell-dependent antigens. In addition to a limited role for classical cognate MHC class II-dependent B cell-T cell interactions in regulating T cell-independent glycan responses, non-follicular innate-like B cell subpopulations make a major contribution to these responses. Understanding the factors regulating these unique B cell populations is key to improving carbohydrate-based vaccines and therapies.
We are investigating factors important for innate B cell development, activation, proliferation, isotype switching, and differentiation into antibody secreting cells following encounter with carbohydrate antigens derived from bacteria and cancers. We are examining key determinants that modulate antibody production by these cells, including age, adjuvants, immunoinhibitory molecules, and accessory cells.
Ultimately, our goal is to develop an understanding of how anti-carbohydrate antibody responses can be enhanced to provide optimal protection against disease-causing agents in humans.