Professor Kai-Michael Toellner Dr. rer. nat., Dipl.-Biol.

Kai-Michael Toellner

Institute of Immunology and Immunotherapy
Professor of Adaptive Immunology

Contact details

Telephone
+44 (0)121 415 8687
Email
k.m.toellner@bham.ac.uk
View my research portal
Address
Institute of Immunology and Immunotherapy
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Kai Toellner is Professor of Adaptive Immunology at the Institute of Immunology and Immunotherapy and the Cancer and Immunology and Immunotherapy Centre Birmingham.

He studies how lymphocytes differentiate in response to pathogens or vaccines and how this leads to the generation of protective antibodies and long term immune memory. He has published over 70 research papers in international journals and received major grants from the European Union, Pfizer, the MRC and BBSRC.

Qualifications

  • Dr. rer. nat., Biochemistry “Studies on the Physiology of Follicular Dendritic Cells and Germinal Centre T cells” Forschungszentrum Borstel, University of Hohenheim, 1994
  • Dipl.-Biol. Biology 1990

Biography

Professor Kai-Michael Toellner studied biology at the University of Hohenheim, Germany, where he had his first contact with immunology in the laboratory of Clinical Chemistry and Laboratory Medicine, Katharinenhospital Stuttgart, working on new flow cytometry techniques to measure lymphocytes in cerebrospinal fluid. From there he moved to the Forschungszentrum Borstel, Germany, for a PhD project on the regulation of germinal centre reactions by T lymphocytes and cytokines under the mentorship of Professor Johannes Gerdes.

In 1994, Kai Toellner started as a postdoctoral research fellow at the Department of Immunology, University of Birmingham, initially under the mentorship of Professor Ian MacLennan and later with his own research team. 

His main interests are cellular interactions and differentiation processes that happen in lymphoid tissues during cellular responses to vaccines or pathogens. During these processes lymphocytes differentiate to become high affinity effector cells that will produce pathogen-specific neutralizing antibody and form immunological memory that can protect us over a long time. Processes studied are the role of cytokines produced by T lymphocytes and stroma onto the selection and differentiation of B lymphocytes, the role of antibody and B cell receptor signals on the selection of B cells in germinal centres, and which signals regulate output of effector B cells from the germinal centre, i.e. cytokines, chemokines, and accessory cells regulating differentiation of high affinity plasma cells and memory B cells.

He has active collaborations with several labs in the UK, Germany, Italy, and Australia. 

Teaching

Teaching Programmes

Postgraduate supervision

Kai is interested in supervising doctoral research students in the following areas:

  • Signals regulating selection of B cells in germinal centres
  • Diurnal effects on antibody affinity maturation
  • Signals leading to differentiation of plasma cells 
  • Regulation of B cell migration by chemokines

If you are interesting in studying any of these subject areas please contact Professor Kai-Michael Toellner directly, or for any general doctoral research enquiries, please email mds-gradschool@contacts.bham.ac.uk.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings.

Research

Research themes

Immunology

Research activity

Selection of B cells in germinal centres

Most antibody responses involve affinity maturation. This process occurs in germinal centres (GCs), microanatomical structures in lymphoid tissues where B lymphocytes mutate and mature their immunoglobulin V-genes. Affinity maturation is thought to be achieved by Darwinian evolution with repeated cycles of Ig hypermutation followed by B cell interaction with the antigen that is on follicular dendritic cells. This is then followed by stimulation from follicular T helper cells. We are studying how antigen, antibodies, T cells and other accessory cells in germinal centre interact with B cells and provide stimulation or barriers that lead to selection of higher affinity B cells. Main focus of this work is to understand the action of vaccines, and to understand processes that become defunctional during ageing.

Regulation of immunoglobulin class switching and plasma cell differentiation

B cells not only mutate their antibody genes after contact with antigen, they also rearrange these genes to produce antibody switch variants with same specificity, but different function. This process is called immunoglobulin class switching and happens in B cells at different stages and in different microanatomical compartments during an antibody response. The end product of B cell differentiation is the plasma cell – a cellular factory specialised in producing large amounts of antibody. Similar microenvironments and signals to the ones that induce immunoglobulin class switching also regulate plasma cell differentiation.

We are trying to understand the molecular signals that lead to these processes and the cellular interactions that provide signals for immunoglobulin class switching or plasma cell differentiation.

T helper lymphocyte differentiation

T helper cells are the main cells that interact with B cells and regulate antibody responses, having a role not only in the initiation of B cell differentiation, but also for long term immunological memory. We are interested in the differentiation of specialized subsets of T cells regulating B cell differentiation, and in the development and distribution of memory T cells throughout different microanatomical compartments.

Publications

Recent publications

Article

Petersone, L, Wang, CJ, Edner, NM, Fabri, A, Nikou, S-A, Hinze, C, Ross, EM, Ntavli, E, Elfaki, Y, Heuts, F, Ovcinnikovs, V, Rueda Gonzalez, A, Houghton, LP, Li, HM, Zhang, Y, Toellner, K-M & Walker, LSK 2023, 'IL-21 shapes germinal center polarization via light zone B cell selection and cyclin D3 upregulation', The Journal of Experimental Medicine, vol. 220, no. 10, e20221653. https://doi.org/10.1084/jem.20221653

Jossi, S, Arcuri, M, Alshayea, A, Persaud, R, Marcial Juarez, E, Palmieri, E, Di Benedetto, R, Perez-Toledo, M, Pillaye, J, Channell, W, Schager, A, Lamerton, R, Jones, C, Goodall, M, Haneda, T, Bäumler, AJ, Jackson-Jones, LH, Toellner, K, MacLennan, C, Henderson, I, Micoli, F & Cunningham, A 2023, 'Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses', Frontiers in immunology, vol. 14, 1139329. https://doi.org/10.3389/fimmu.2023.1139329

Zhang, Y & Toellner, K-M 2022, 'Germinal center derived B cell memory without T cells', The Journal of Experimental Medicine, vol. 219, no. 3, e20220012. https://doi.org/10.1084/jem.20220012

Zhang, Y, Garcia-Ibanez, L, Ulbricht, C, Lok, LSC, Pike, JA, Mueller-Winkler, J, Dennison, TW, Ferdinand, JR, Burnett, CJM, Yam-Puc, JC, Zhang, L, Alfaro, RM, Takahama, Y, Ohigashi, I, Brown, G, Kurosaki, T, Tybulewicz, VLJ, Rot, A, Hauser, AE, Clatworthy, MR & Toellner, K-M 2022, 'Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift', Nature Communications, vol. 13, no. 1, 2460. https://doi.org/10.1038/s41467-022-29978-y

Penny, HA, Domingues, RG, Krauss, MZ, Melo-Gonzalez, F, Lawson, MAE, Dickson, S, Parkinson, J, Hurry, M, Purse, C, Jegham, E, Godinho-Silva, C, Rendas, M, Veiga-Fernandes, H, Bechtold, DA, Grencis, RK, Toellner, K-M, Waisman, A, Swann, JR, Gibbs, JE & Hepworth, MR 2022, 'Rhythmicity of intestinal IgA responses confers oscillatory commensal microbiota mutualism', Science Immunology, vol. 7, no. 75, eabk2541. https://doi.org/10.1126/sciimmunol.abk2541

Yam-Puc, JC, Zhang, L, Maqueda Alfaro, R, Garcia Ibanez, L, Zhang, Y, Davies, J, Senis, Y, Snaith, M & Toellner, K 2021, 'Enhanced BCR signaling inflicts early plasmablast and germinal center B cell death', iScience, vol. 24, no. 2, 102038, pp. 102038. https://doi.org/10.1016/j.isci.2021.102038

Jennings, E, Elliot, T, Thawait, N, Kanabar, S, Yam-Puc, JC, Ono, M, Toellner, K-M, Wraith, DC, Anderson, G & Bending, D 2020, 'Nr4a1 and Nr4a3 reporter mice are differentially sensitive to T cell receptor signal strength and duration', Cell Reports, vol. 33, no. 5, 108328. https://doi.org/10.1016/j.celrep.2020.108328, https://doi.org/10.1016/j.celrep.2020.108328

Roco, J, Mesin, L, Binder, SC, Nefzger, C, Gonzalez-Figueroa, P, Canete, PF, Ellyard, J, Shen, Q, Robert, PA, Cappello, J, Vohra, H, Zhang, Y, Nowasad, CR, Schiepers, A, Corcoran, LM, Toellner, K, Polo, JM, Meyer-Hermann, M, Victora, GD & Vinuesa, CG 2019, 'Class-switch recombination occurs infrequently in germinal centers', Immunity, vol. 51, no. 2, pp. 337-350.e7. https://doi.org/10.1016/j.immuni.2019.07.001

Darby, MG, Chetty, A, Mrjden, D, Rolot, M, Smith, K, MacKowiak, C, Sedda, D, Nyangahu, D, Jaspan, H, Toellner, KM, Waisman, A, Quesniaux, V, Ryffel, B, Cunningham, AF, Dewals, BG, Brombacher, F & Horsnell, WGC 2019, 'Pre-conception maternal helminth infection transfers via nursing long-lasting cellular immunity against helminths to offspring', Science Advances, vol. 5, no. 5, eaav3058. https://doi.org/10.1126/sciadv.aav3058

Flores-Langarica, A, Müller Luda, K, Persson, EK, Cook, CN, Bobat, S, Marshall, JL, Dahlgren, MW, Hägerbrand, K, Toellner, KM, Goodall, MD, Withers, D, Henderson, IR, Johansson Lindbom, B, Cunningham, A & Agace, WW 2018, 'CD103+CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin', Mucosal immunology, vol. 11, no. 3, pp. 681-692. https://doi.org/10.1038/mi.2017.105

Schager, A, Dominguez-Medina, CC, Necchi, F, Micoli, F, Goh, YS, Goodall, M, Flores-Langarica, A, Bobat, S, Cook, C, Arcuri, M, Marini, A, King, LDW, Morris, F, Anderson, G, Toellner, K-M, Henderson, I, López-Macías, C, MacLennan, CA & Cunningham, A 2018, 'IgG Responses to Porins and Lipopolysaccharide within an Outer Membrane-Based Vaccine against Nontyphoidal Develop at Discordant Rates', mBio, vol. 9, no. 2, e02379-17. https://doi.org/10.1128/mBio.02379-17, https://doi.org/http://mbio.asm.org/content/9/2/e02379-17, https://doi.org/10.1128/mBio.02379-17

Zhang, Y, Tech, L, George, LA, Acs, A, Durrett, RE, Hess, H, Walker, LSK, Tarlinton, DM, Fletcher, AL, Hauser, AE & Toellner, K-M 2018, 'Plasma cell output from germinal centers is regulated by signals from Tfh and stromal cells', The Journal of Experimental Medicine, vol. 215, no. 4, pp. 1227-1243. https://doi.org/10.1084/jem.20160832

Toellner, K-M, Sze, D & Zhang, Y 2018, 'What are the primary limitations in B cell affinity maturation? How much affinity maturation can we drive with vaccination? A role for antibody feedback', Cold Spring Harbor Perspectives in Biology, vol. 10, no. 5, a028795. https://doi.org/10.1101/cshperspect.a028795, https://doi.org/10.1101/cshperspect.a028795

Preprint

Jossi, SE, Arcuri, M, Alshayea, A, Persaud, RR, Marcial-Juárez, E, Palmieri, E, Benedetto, RD, Pérez-Toledo, M, Pillaye, J, Channell, WM, Schager, AE, Lamerton, RE, Cook, CN, Goodall, M, Haneda, T, Bäumler, AJ, Jackson-Jones, LH, Toellner, K-M, MacLennan, CA, Henderson, IR, Micoli, F & Cunningham, AF 2023 'Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses' bioRxiv. https://doi.org/10.1101/2023.01.03.522561

Review article

Yam-Puc, JC, Zhang, L, Zhang, Y & Toellner, KM 2018, 'Role of B-cell receptors for B-cell development and antigen-induced differentiation', F1000Research, vol. 7, 429. https://doi.org/10.12688/f1000research.13567.1

View all publications in research portal