RESEARCH PROJECTS
Memory B Cell Mechanisms in Host Defense
BACKGROUND
Protein vaccination is an effective public health initiative in the prevention of infectious disease and a safer alternative to the classical use of attenuated microorganisms. In this context, protein vaccination aims to prime adaptive immunity to anticipate future pathogen exposure by generating antigen-specific immune memory. Most effective vaccines rely heavily on long-term protection of high-affinity B cell memory that develops under the antigen-specific guidance of helper T cells.
Our laboratory has a long-standing commitment to understanding the cellular dynamics and molecular control of helper T cell regulated B cell Immunity. We believe that the next generation of vaccines will require a new level of understanding of immune system mechanisms and how they work to protect from infection. Our research program focuses on the regulatory mechanisms used by follicular helper T cells to program effective and protective high-affinity B cell memory.
MEMORY B CELLS
Basic ongoing studies dissect the programming of memory B cells after initial priming and antigen re-challenge. We provide evidence that the rate of affinity maturation within germinal centers is influenced by the vaccine adjuvant. This observation is being pursued at the mechanistic level to elucidate pathways within antigen-responsive B cells and TFH cells that control the quality and quantity of B cell memory. We aim to test the protective value of primary adjuvant formulation on protein vaccine-induced immune protection against infectious challenge.
FOLLICULAR HELPER T CELLS
It is important to remember and emphasize that the memory B cell response to protein antigen re-challenge require cognate T cell help. Hence, the vaccine boost becomes an important means for modifying and potentially enhancing the quality of memory TFH regulated memory B cell function. While a boost is used in every protein vaccine regime, the mechanisms that control this phase of memory B cell fate remain unknown. The impact of the boost on long-term immune protection from infectious challenge is a major focus of our current research program.
INNATE REGULATION OF TFH DEVELOPMENT
We have recently extended our general strategy for studying antigen-responsive lymphocytes to the isolation of peptide-MHCII expressing dendritic cell compartments directly ex vivo. Using mAbs for specific pMHCII-complexes, we reveal major subsets of pMHCII-expressing DC that migrate to the draining lymph nodes after local priming. Using antibody blocking and conditional genetic ablation, we aim to dissect the innate molecular regulators of TFH programming.These studies aim to enhance adjuvant formulation based on the molecular mechanisms of innate immunity and their impact on long-term immune protection from infectious challenge.
