Opening up the research toolkit

In 2024, Professor Kai-Michael Toellner joined the Institute’s Immunology programme after 30 years at the University of Birmingham’s Institute of Immunology and Immunotherapy. We find out what drew him from the UK’s second-largest city to the Babraham Research Campus, the pressing questions he wants to answer, and why it’s vital we understand more about how our immune system works.

Immunisation is a global health success story. It saves millions of lives every year, helps control outbreaks of infectious diseases such as Covid, and is a vital defence against microbial resistance. Despite this—and a history dating back hundreds of years—much of how our immune system works at a molecular and cellular level remains to be discovered.

Many gaps in our knowledge exist because the immune system is extraordinarily complex, involving myriad communications between multiple components. But deepening our understanding is crucial if we are to develop more and better vaccines, including against diseases such as cancer, tackle autoimmune diseases, and find out why our immune system works less well as we age.

Professor Kai-Michael Toellner has studied the biology of the immune system and how it responds to vaccination and infection for over 30 years. “We want to understand how our bodies react to infection and vaccination,” he says. “Vaccination essentially mimics an infection in non-dangerous way. And we’re interested in how the body makes antibodies to that, and ultimately how the body remembers exposure, something we call immune memory.”

Toellner and his team work on B cells, part of the so-called adaptive arm of the immune system. Some B cells produce antibodies in response to active infection while others, known as memory B cells and plasma cells, act as our immunological memory. These long-lived cells remember past infections or immune priming through vaccination so they can respond rapidly and robustly the next time they encounter the same infection.

“It’s a very complex process,” Toellner explains. “The main focus of our research is germinal centres. These are structures in lymphoid tissues where clusters of dividing B cells are found. When the immune system encounters an infection or vaccination, it’s here that B cells respond by dividing, mutating, and then selecting the fittest variants, a process that is essentially Darwinian evolution on a cellular level.”

Several other cell types help regulate this process, including follicular dendritic cells, which keep antigens in place. This provides a training ground for B cell selection. Also present in the germinal centre are T cells which stimulate the B cells and give them the right signals, and macrophages which clean up the many unsuitable cells that are not fit for selection and do not survive.

Teasing apart this complex system requires a top-notch toolkit, which is one of the Institute’s key strengths. “One of the things that attracted me to the Institute is its excellent facilities, and the huge amount of experience here in the mouse models I use,” he says. “Doing cutting-edge research requires the best equipment, from flow cytometry to cell sorting and genomics. Being here really enhances my toolkit.”

He is also enjoying other aspects of his new environment: the Institute’s positive and collaborative nature, its proximity to existing academic and biotech collaborators in Cambridge and Granta Park, and the prospect of building new partnerships. “The strength of the biotech community here is a huge plus, so I’m keen on setting up new collaborations,” he says.

While Toellner’s focus is on fundamental science, advances in the field will feed into far-reaching practical applications, including new treatments for cancer and autoimmune diseases, and new strategies for healthier ageing.

New vaccines that trigger our immune system to produce its own antigens against cancer, for example, are of major interest and could bring many benefits. The team have had a longstanding interest in using the immune response to eliminate cancer cells in the same way as it identifies and attacks infected cells. “We are looking at certain antigens that are expressed in tumours and tumour vessels and working out ways of triggering antibody responses by the host itself,” explains Toellner. “If we can develop vaccines to elicit an immune response against the tumour, this would be cheaper than cellular therapies, opening up more affordable treatments for cancer patients in the global south.”

Another potential application stems from a chance discovery by Toellner and his biotech collaborators. In an unexpected outcome, they produced a mouse in which all B cells are switched off. B cells recognising our body’s own cells must be inactivated to protect the body from its own immune system and prevent autoimmune diseases, but with age this control can fail. “Interestingly, as these mice age they spontaneously start to make autoimmune responses, so this may offer us a way of studying autoimmunity in ageing,” he says.

While his focus remains firmly on the fundamentals, his research illustrates how crucial fundamental research is in the pipeline linking new ideas, new knowledge and—ultimately—new applications to promote healthier ageing. “Our focus is on the fundamental question of how the body reacts to foreign antigens. Without understanding this you can’t understand vaccination or autoimmunity,” Toellner concludes. “Only when you start understanding this process better, can you start trying to improve it.”