Immune cells must learn not to attack the body itself. A team of researchers from the Technical University of Munich (TUM) and the Ludwig Maximilian University of Munich (LMU) has discovered an unknown mechanism behind this: other immune cells, B cells, contribute to the “training” of T cells. . in the thymus gland. If this process fails, autoimmune disease can develop. The study confirms this for Neuromyelitis optica, a disease similar to multiple sclerosis. Other autoimmune diseases may also be linked to the failure of this new mechanism.

In children and adolescents, the thymus gland acts as a “school for T cells.” Our chest organ is where the precursors of T cells that later attack the body’s own cells are disposed of. Epithelial cells in the thymus present a large number of molecules found in the body to future T cells. If any of them react to these molecules, a self-destruction program is triggered. T cells that attack the body’s own molecules that persist and multiply, on the other hand, can cause autoimmune diseases.

A new mechanism was discovered.

I The natureThe team, led by Ledger Klein, Professor of Experimental Neuroimmunology at TUM and a Principal Investigator in the SyNergy Cluster of Excellence, and Professor of Immunology at LMU’s Biomedical Center (BMC), explains another unknown mechanism behind this. Is.

In addition to T cell precursors, the thymus gland also contains other immune cells, the B cells. They develop in the bone marrow but migrate to the thymus in early childhood. “The function of B cells in the thymus gland has been a mystery that has puzzled immunologists for many years,” says Thomas Korn. Researchers have now been able to show for the first time that B cells play an active role in teaching T cells which target not to attack.

A disease like MS due to a defect in the formation of tolerance

Neuromyelitis optica is an autoimmune disease similar to multiple sclerosis (MS). Although it is not yet known which molecules are attacked in MS, it is well established that T cells respond to the protein AQP4 in neuromyelitis optica. AQP4 is most prominently expressed in nerve tissue cells, which then become targets of autoimmunity. Often, the optic nerve is affected.

The researchers were able to show that not only epithelial cells but also B cells in the thymus gland of humans and mice express AQP4 and present it to T cell precursors. If B cells were prevented from doing so in animal experiments, AQP4-reactive T cell progenitors were not killed and autoimmune disease developed. This was also the case when epithelial cells still presented the molecule. The team concludes from this that B cells in the thymus are a prerequisite for immune tolerance to AQP4.

Protection against subsequent interactions between T cells and B cells

“We suspect that this previously unknown process has evolved specifically to prevent dangerous interactions between autoreactive T and B cells in the lymph nodes and spleen, the so-called peripheral immune compartment,” says Ludger Klein. Once the immune system is developed, B and T cells can communicate and thus trigger a highly effective immune response. This is useful when it comes to quickly fighting pathogens. However, on occasion, B cells can mistakenly present the body’s own proteins, such as AQP4. If AQP4-reactive T cells are not resolved in the thymus, this can lead to a sudden and violent massive invasion of the body.

Possible cause of other immune disorders

“We hypothesize that problems with the training of T cells by B cells in the thymus may also cause other autoimmune diseases,” says Thomas Korn. “Finally, B cells in the thymus present a whole range of the body’s own proteins. Further studies investigating the relevant interactions are warranted.”

According to the researchers, possible suspects include antiphospholipid syndrome (APS) and some forms of cerebral amyloid angiopathy. “Looking to the future, this interaction in the thymus could be used to treat existing autoimmune diseases,” says Thomas Korn.