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We study the cellular interactions and molecular events that lead to the development of high affinity and protective antibodies during humoral immune responses. Our main focus is the germinal centre reaction.

About the Research

The quality of antibodies improves over the course of immune responses due to a remarkable process known as antibody affinity maturation, which occurs in germinal centres (GCs). GCs are transient structures that develop within local secondary lymphoid tissues such as lymph nodes. Here, B cells “evolve” their antibody genes through iterative rounds of somatic mutations and selection. B cells acquiring damaging mutations are deleted, while cells carrying nucleotide changes that enhance antigen binding are preferentially expanded. Despite its fundamental importance in acquired immunity, the cellular and molecular events responsible for selection remain incompletely understood. This is particularly true when selection is considered in the context of infections rather than simpler model systems. Most pathogens display a plethora of epitopes and the best neutralization sites are commonly “challenging” targets. For example, broadly neutralising antibodies against HIV develop in germinal centres, but only infrequently, and only after months or years of acquiring mutations. These problems are discussed in more depth in Bannard and Cyster, Curr. Opin. Immunol. 2017 (PMID: 28088708). As such, the mechanisms driving clonal evolution in GCs are not only scientifically fascinating but also directly relevant for developing novel vaccines.

Projects in the Bannard laboratory focus around trying to decipher the fundamental biology underpinning the development of humoral immunity. We investigate the cellular interactions and regulatory mechanisms that facilitate antibody affinity maturation. We aim to understand what “selection” entails, and we hope to determine how cells make fate choices such as when to differentiate into memory and antibody secreting plasma cells. There may also be opportunities to study why humoral immunity suboptimal and slow to develop during malaria infections. To reach these goals, we employ a wide range of cutting-edge techniques such as high-end flow cytometry, confocal microscopy, live cell imaging (e.g. multi-photon microscopy), single B cell cloning and next generation sequencing. Our work relies heavily on sophisticated genetically modified in vivo systems and we often use live infections (e.g. Influenza A). As such, students can expect to receive sound intellectual and practical science training.

Informal enquiries are welcomed and can be directed to Oliver Bannard.

Training Opportunities

Project will be based in the Bannard lab in the Weatherall Institute of Molecular Medicine (WIMM). This is a small group and so students will benefit from frequent interactions with their supervisor. Training in various cutting edge technologies will be provided.

 

Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence, and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

 

Publications

1

Stewart, I., Radtke, D., Phillips, B., McGowan, S. J., & Bannard, O. (2018). Germinal Center B Cells Replace Their Antigen Receptors in Dark Zones and Fail Light Zone Entry when Immunoglobulin Gene Mutations are Damaging. Immunity, 49(3), 477–489.e7.

2

Radtke, D., & Bannard, O. (2018). Expression of the Plasma Cell Transcriptional Regulator Blimp-1 by Dark Zone Germinal Center B Cells During Periods of Proliferation. Frontiers in Immunology, 9, 3106.

3

Bannard, O., and Cyster, J.G. (2017). Germinal centers: programmed for affinity maturation and antibody diversification. Curr. Opin. Immunol. 45, 21–30.

4

Bannard, O., McGowan, S.J., Ersching, J., Ishido, S., Victora, G.D., Shin, J.-S., and Cyster, J.G. (2016). Ubiquitin-mediated fluctuations in MHC class II facilitate efficient germinal center B cell responses. J. Exp. Med. 213, 993–1009.

5

Bannard, O., Horton, R.M., Allen, C.D.C., An, J., Nagasawa, T., and Cyster, J.G. (2013). Germinal center centroblasts transition to a centrocyte phenotype according to a timed program and depend on the dark zone for effective selection. Immunity 39, 912–924.

6

Bannard, O., Kraman, M., Fearon, D.T. (2009). Secondary replicative function of CD8+ T cells that had developed an effector phenotype. Science, 323(5913):505-509.









Supervisors