Grant: Project Grant

Memory B cells are pivotal to the establishment and maintenance of protection from re-encountered pathogens, both in the context of natural infection and vaccination. Following activation memory B cells divide and differentiate into antibody-secreting plasma cells more rapidly than naïve B cells. The importance of pathogen-specific antibodies is emphasized by observations illustrating that neutralizing antibody responses are an important component of most successful vaccines. It is therefore of critical importance to identify mechanisms regulating memory B cell responses. The Fc Receptor-Like (FCRL) family of cell surface receptors is preferentially expressed on B lineage cells. Among these, FCRL4 family member is expressed only on a subpopulation of memory B cells that are functionally impaired in chronic infectious diseases like HIV. In previous work, we could demonstrate the strong regulatory activity of FCRL4 on memory B cells. Furthermore, we determined that antibodies encoded by FCRL4+ memory B cells preferentially detect commensal microbiota. In this research proposal we will investigate the antibodies to known antigens from vaccinations that are encoded by FCRL4+ and FCRL4- memory B cells. We will determine the factors that lead to the generation of FCRL4-bearing memory B cells and we will investigate the characteristics antibody secreting plasma cells derived from FCRL4+ and FCRL4- memory B cells. The results from this study will provide deeper understanding of functionally distinct memory B cell populations and their plasma cell progeny. Ultimately, this information will be important in vaccine design efforts aiming to elicit long lasting protective antibody titres to pathogens to which presently no effective vaccines are available.