Karen M. Haas, PhD
Professor, Department of Microbiology and Immunology; Department of Cancer
My 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 (ie., Streptococcus pneumoniae and Haemophilus influenzae), 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.
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 infection and cancer. Antibody responses to carbohydrate antigens often proceed in the absence of T cell help, and are thus referred to as T cell independent (TI) antibody responses. A growing body of evidence supports the concept that TI antibody responses are regulated in a manner that is distinct from T cell dependent (TD; typically protein) antibody responses. In addition to the limited role for cognate B cell-T cell interactions in regulating these responses, non-follicular B cell subpopulations contribute to these responses. Understanding the factors regulating these unique innate-like B cell populations is key to improving carbohydrate-based vaccines.
In mice, B-1b cells represent a key B cell subset identified to play a major role in TI antibody responses. We have identified a population of B-1b-like cells in non-human primates that responds to TI antigens in a manner analogous to murine B-1b cells. The presence of B-1b cells in non-human primates supports the possibility that these cells also exist in humans. We are therefore interested in understanding the factors involved in regulating B-1b cell activation, proliferation, isotype switching, and differentiation into antibody secreting cells following encounter with carbohydrate antigens. 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.