Microenvironmental Regulation of Antibody Responses

Group leads: Adam Cunningham, Ian MacLennan, Antal Rot, Kai Toellner

B lymphocytes are the cells that will generate antibodies – proteins that convey memory and specifically protect us from anything foreign that we encounter during contact with pathogens or during vaccination. B lymphocytes develop as clones of cells that are tuned to specifically produce antibodies against one certain structure. During an immune response B cell clones evolve their genes that code for specificity to a single foreign moiety to become extremely highly specific and affine for this foreign structure. This differentiation process involves B cells migrating in response to chemokines through various microanatomical compartments, in the process interacting with a range of accessory cells. Our research group is studying this differentiation process in response to bacteria (e.g. Salmonella, an organism that kills 1000s of children in developing countries each year), viruses, or model protein antigens. We are trying to understand molecular cues driving B cell compartementalization, cellular interactions in various microanatomical compartments, and the timing and regulation of antibody gene maturation (hypermutation and selection) and variation (immunoglobulin class switching) in the development of these responses. Understanding this better should lead to the development of better vaccines, e.g. children to be protected from childhood diseases, or elderly who do not respond very well to vaccines that are in current use.