Antibody affinity maturation in germinal centres during influenza A infection
Supervisors: Dr. Oliver Bannard and Professor Alain Townsend
The quality of antibodies improves over the course of immune responses through antibody affinity maturation. This remarkable process occurs in transient structures called germinal centres that form in the B cell follicles of local lymphoid tissues. Affinity improvements occur through iterative rounds of random immunoglobulin gene somatic hypermutation and competition based “selection". Non-productive mutations are screened out, while cells carrying nucleotide changes that improve antibody-antigen binding abilities are preferentially expanded (selection). Despite its fundamental importance in acquired immunity, the molecular and cellular events involved in selection remain incompletely understood. This is especially true in the context of “real” infections where antigens are more complex than is often the case in model systems. Most pathogens carry a plethora of epitopes and the best neutralization sites are commonly challenging targets. By understanding the fundamental processes underpinning antibody affinity maturation, we hope to gain insight into how to develop better vaccines against important pathogens. This problem is discussed in more depth in Bannard and Cyster, Curr. Opin. Immunol. 2017 (PMID: 28088708).
The goal of this project will be to interrogate the molecular and cellular processes occurring in germinal centres that lead to the development and selection of potent anti-viral antibodies during influenza A infection. Findings from this work are likely to be applicable to humoral responses in general.
This project will be based in the Bannard lab in the MRC Weatherall Institute of Molecular Medicine (WIMM) but will involve close interactions with Professor Alain Townsend (based at the same site). As such, the project will benefit from expertise in basic B cell biology/immunology, antibody characterization and influenza virology. The project is likely to involve the development and use of sophisticated genetically modified host/viral model systems. There will be opportunities to learn and implement cutting edge imaging, sequencing, single B cell cloning and flow cytometry technologies. As such, students can expect to receive sound intellectual and practical science training.
For further information please contact: Dr Oliver Bannard