How antibodies work

Immune defence and autoaggression are controlled by the same mechanism

For humans, antibodies are essential to life: they destroy pathogens and can therefore be used in medicine, for example for therapies to fight cancer. However, sometimes their destructive mechanisms also turn against the very body they inhabit. This results in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Research scientists from the Department for Genetics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have now discovered how antibodies work and what controls them. On the one hand, their findings could provide the basis for the development of more clearly targeted therapies to help combat cancer. On the other hand, they offer new approaches for the treatment of autoimmune diseases. The researchers’ findings were published in the internationally renowned medical journal “Immunity”¹.

“Antibodies are protein molecules and we distinguish fundamentally between two different types”, explains Prof. Dr. Falk Nimmerjahn, chair of the Department for Genetics at FAU and head of the research team. “On the one hand, there are antibodies which possess positive properties which are, for example, used in cancer therapy. On the other hand, there are antibodies known as auto-antibodies which attack the body and trigger illnesses such as systemic lupus erythematosus”. One of the most important discoveries in recent years has been that both types of antibodies are controlled by the same molecules and cellular mechanisms.

The human body is able to produce antibodies which can destroy any type of cell – such as tumour cells for example. Today, modern medicine takes advantage of this particular ability: experts can isolate the cells which produce antibodies and keep them in cell cultures. Here, the cells continue to produce antibodies which are then extracted by doctors and subsequently introduced back into the patient’s body via an infusion or injection where they carry out their therapeutic effect. Due to their small size the antibodies automatically migrate into practically every type of tissue. This is of great advantage to doctors as it means that the antibodies do not have to be injected directly into one or several tumours.

Exactly how antibodies manage to destroy almost all cell types had remained a mystery until now. Previously researchers hypothesised that they interacted with cells referred to as scavenger cells or “natural killer cells”. However, Dr. Markus Biburger and Susanne Aschermann from the Department for Genetics are now able to reveal that an entirely different cell population is responsible for this: monocytes. Once monocytes had been removed from the model, antibodies were neither capable of producing a therapeutic effect against cancer nor were auto-antibodies able to attack the body’s own cells. “Our findings provide numerous approaches for optimising tumour therapy and fighting against autoimmune diseases more effectively”, says Prof. Nimmerjahn. “This allows us to kill two birds with one stone”.

¹Biburger et al., Monocyte Subsets Responsible for Immunoglobulin G-Dependent Effector Functions In Vivo, Immunity (2011), DOI:10.1016/j.immuni.2011.11.009

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