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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

Germinal centres (GCs) are unique transient structures that develop within the B cell follicles of local secondary lymphoid tissues during immune responses. GCs are where high affinity antigen-specific antibodies develop, as well as where long-lived memory B cells and plasma cells are made. The antibodies and cells made in GCs are responsible for conferring much of the immunity elicited by immunisation. The GC response is unique in mammalian biology because it is the only time/place where cells deliberately mutate their genomes. This happens to permit B cells to rapidly evolve their antibody (immunoglobulin) genes through a Darwinian-like process of iterative somatic hypermutation and affinity-based clonal selection. On average, GC B cell mutate and are selected approximately once per day. Despite its fundamental importance in acquired immunity, the mechanism that selects GC B cells expressing higher affinity antibody variants remains incompletely understood. One major outstanding question is how GCs balance the opposing needs for selecting both affinity and clonal diversity, because pathogens easily evade antibody responses that are excessively narrow in their focus (discussed in Bannard and Cyster, Curr. Opin. Immunol. 2017 PMID: 28088708). We recently proposed a new “non-binary” selection model based upon discoveries made by a former (Stewart et al. 2018, Immunity PMID 30231983) and a current student (Long et al. 2022, Science Immunology PMID 35275753), however much remains to be worked out. The question of how GC B cells “choose” when to become memory or long-lived plasma cells also needs answering. Addressing these problems will help guide rational vaccine design for shepherding antibodies to recognise particular pathogen-derived antigens/epitopes (such as for HIV broadly neutralising and malaria (Plasmodium)-specific antibodies), and for eliciting higher/more persistent serum antibody titres.

Projects in the Bannard lab focus around trying to decipher the fundamental biological processes underpinning the selection in GCs and the development of humoral immunity. We aim to understand what “selection” entails, and we hope to determine how cells make fate choices. We study cell behaviour within their native tissue context by making use of complex in vivo genetically modified models, cutting edge ex vivo analysis (e.g., single cell RNA-seq, high end flow cytometry, confocal microscopy, single B cell antibody cloning), and live in situ imaging to visualise and track cell behaviour in real time (e.g., 2-photon microscopy, Maclean et al 2022, Immunity PMID 35349789). We study immune responses in the context of infection (e.g., Influenza A virus) and after immunisation. As such, students can expect to tackle fundamental immunology questions, while receiving sound intellectual and practical science training.

Informal enquiries are welcomed and can be directed to oliver.bannard@ndm.ox.ac.uk

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

Long, Z., Phillips, B., Radtke, D., Meyer-Hermann, M., Bannard, O. (2022). Competition for refueling rather than cyclic re-entry evident in germinal centers. Sci. Immunol. 7(69):eamb0775.

2

MacLean AJ, Richmond N, Koneva L, Attar M, Medina CAP, Thornton EE, Gomes AC, El-Turabi A, Bachmann MF, Rijal P, Tan TK, Townsend A, Sansom SN, Bannard O, Arnon TI. Secondary influenza challenge triggers resident memory B cell migration and rapid relocation to boost antibody secretion at infected sites. Immunity. 2022 Apr 12;55(4):718-733.

3

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.

4

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.

5

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

6

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.

7

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.

8

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