Immune memory explained

While the principle of immune memory has been known for decades, the exact molecular mechanisms underpinning it have remained a mystery. Australian scientists have now unraveled part of that mystery, identifying the role of a gene called STAT3, which acts as a kind of roundabout, directing chemical messenger molecules to various destinations.

An infection, or a vaccination, ‘primes’ the immune system, so that when you next encounter the same invader, your body ‘remembers’ it and quickly makes large amounts of exactly the right antibodies to quash the infection.

Once a cell is primed, traffic on the STAT3 roundabout speeds up enormously, as if the road has been upgraded and the signage much improved.

Primed immune cells, known as ‘memory B cells’, behave very differently from ‘naïve B cells’, which have never seen infection. Memory B cells act with great speed and efficiency, removing a pathogen so quickly that people frequently remain unaware they have been infected.

Patients with the rare immunodeficiency disorder, Hyper IgE Syndrome, caused by mutations in the STAT3 gene, have a ‘functional antibody deficiency’. While you can detect antibodies in their blood, those antibodies are not very good at fighting specific diseases or infections.

Through studying the blood cells of Hyper IgE patients over time, Associate Professor Stuart Tangye, Dr Elissa Deenick and Danielle Avery, from Sydney’s Garvan Institute of Medical Research, have gained considerable insight into the STAT3 gene. They recently observed that naïve B cells in Hyper IgE patients barely respond to important signaling molecules, whereas their memory B cells behave in the same way as those of healthy people.

The lab members realised that naïve B cells need a very strong chemical signal indeed – targeting STAT3 – to kick-start antibody production. Conversely, memory B cells only need faint signals to generate a huge antibody response. Even STAT3-compromised memory cells from Hyper IgE patients are functional. This breakthrough finding is published in the Journal of Experimental Medicine, now online.