B cells teach T cells which targets should not be attacked

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 a previously unknown mechanism: other immune cells, B cells, contribute to “the training » of T cells in the thymus gland.

If this process fails, autoimmune diseases can develop. The study confirms this for neuromyelitis optica, a disease similar to multiple sclerosis. Other autoimmune diseases could also be linked to the failure of this new mechanism.

In children and adolescents, the thymus functions as a “T cell school.” Our chest organ is where precursors of T cells that would later attack the body’s own cells are eliminated. The epithelial cells of the thymus present a large number of molecules present in the body to future T lymphocytes. If one of them reacts to one of these molecules, a self-destruct program is triggered.

On the other hand, T lymphocytes which attack the body’s own molecules while remaining intact and multiplying can cause autoimmune diseases.

In NatureThe team led by Thomas Korn, professor of experimental neuroimmunology at TUM and principal investigator of the SyNergy Excellence Group, and Ludger Klein, professor of immunology at LMU Biomedical Center (BMC), describe another previously unknown mechanism behind that.

In addition to the precursors of T lymphocytes, the thymus also contains other immune cells, B lymphocytes. They develop in the bone marrow but migrate to the thymus from early childhood. “The function of B cells in the thymus is a mystery that has intrigued immunologists for many years,” explains Thomas Korn. The researchers were able to show for the first time that B cells play an active role in teaching the targeting T cells not to attack.

MS-like disease due to a dysfunction 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 AQP4 protein in neuromyelitis optica. AQP4 is mainly expressed in cells of nervous tissue, which then become the target of the autoimmune reaction. The optic nerve is frequently affected.

The researchers were able to show that in the thymus of humans and mice, not only epithelial cells but also B cells express and present AQP4 to T cell precursors. If B cells were prevented from doing so during In animal experiments, AQP4-reactive T cell precursors were not cleared and the autoimmune disease developed. This was also the case when the epithelial cells still presented the molecule.

The team concludes that thymus B cells are a necessary condition for immune tolerance to AQP4.

“We suspect that this previously unknown process evolved in particular to prevent dangerous interactions between self-reactive T and B cells in the lymph nodes and spleen, the so-called peripheral immune compartment,” explains Ludger Klein.

Once the immune system is developed, B and T cells can communicate and thus trigger very effective immune reactions. This is useful when it comes to quickly combating pathogens. However, sometimes B cells accidentally present the body’s own proteins, such as AQP4. If the AQP4-responsive T cells had not been sorted into the thymus, this could lead to a sudden and violent large-scale attack on the body.

Possible cause of other immune disorders

“We assume that problems with the formation of T cells by B cells in the thymus can also cause other autoimmune diseases,” explains Thomas Korn. “After all, B cells in the thymus exhibit a whole range of proteins unique to the organism. The corresponding interactions need to be investigated in further studies.”

Likely suspects, researchers say, include antiphospholipid syndrome (APS) and some forms of cerebral amyloid angiopathy. “In the longer term, this interaction in the thymus could be exploited to treat existing autoimmune diseases in a very targeted manner,” explains Thomas Korn.