How B and T cells fuel the disease process in MS

Around 280,000 to 300,000 people in Germany live with multiple sclerosis (MS) – and the trend is rising. This chronic inflammatory autoimmune disease is characterized by the body's immune system attacking the protective sheath surrounding the nerve fibers, known as the myelin sheath.

In many MS patients, large accumulations of immune cells, especially B and T cells, form under the meninges. These ectopic lymphoid structures (eLFs) are cellular accumulations of the immune system that form outside the classic lymphatic organs such as lymph nodes or spleen in meningeal follicles.

"The function of these meningeal follicles was previously unclear," says Dr. Anneli Peters from the Biomedical Center, Institute for Clinical Neuroimmunology, LMU. "In our model, we have now been able to show that B and T cells cooperate intensively in these structures, leading to the maturation and activation of autoreactive immune cells." The new study thus provides initial evidence that meningeal follicles could continuously fuel inflammatory processes in the central nervous system. The researchers have published their findings in Science Immunology.

Background: Doctors are familiar with eLFs in tumor diseases, where they play a role in defending against cancer cells. Why these structures also form in the brain and spinal cord of people with severe MS is unknown.

One reason for this lack of knowledge is that eLFs can usually only be detected in postmortem histopathological examinations. This makes it difficult to record and understand their exact function and development in MS.

Using a mouse model, researchers led by Anneli Peters were able to gain important insights. They transferred special T helper cells, which recognize myelin oligodendrocyte glycoprotein (MOG) and had previously been differentiated in vitro into interleukin 17-producing TH17 cells, to immunocompetent mice. MOG is a protein found in the myelin sheath of nerve cells. The researchers thus triggered an MS-like disease in mice, known as experimental autoimmune encephalomyelitis, in which eLFs form.

"Using high-resolution live imaging, we were able to detect direct and prolonged contacts between TH17 T cells and B cells in the eLFs," said Peters. This interaction led to the reactivation of autoreactive T cells—a process that further drives chronic inflammation in the central nervous system (CNS).

T cells and B cells are linked in a kind of mutual dependency: T cells in the CNS need the support of B cells to maintain a pro-inflammatory cytokine profile. Conversely, T cells promote the differentiation and proliferation of B cells—a mutual reinforcement that sustains smoldering inflammation in the CNS.

Interestingly, eLFs originally originate from highly active B cells that migrate into the CNS. "We observed that B cells in the eLFs begin to mature and multiply clonally under TH17 cell stimulation—they respond to signals from T cells," said Peters. Even though B cells migrate into the CNS later than TH17 cells, they can reactivate autoreactive T cells there and enhance their inflammatory responses via antigen presentation.

Prospects for new therapies

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The discovery that T and B cells cooperate closely in eLFs and reinforce each other's activity opens up new therapeutic possibilities in the medium term. ‘Our results suggest that this co-dependence could be a promising target for new treatment approaches in autoimmune diseases such as multiple sclerosis,’ says Peters.

Follow-up studies are in progress. ‘We want to investigate the exact mechanism of immune cell activation in the meningeal follicles and understand which signalling pathways are important for the formation of these structures,’ explains the scientist. ‘It is also very important for us now to investigate as thoroughly as possible the extent to which the results from our model can be transferred to MS patients.’

Anna Kolz, Clara de la Rosa, Isabel J. Syma, Sarah McGrath, Vladyslav Kavaka, Rosa Schmitz, Anna S. Thomann, Martin Kerschensteiner, Eduardo Beltran, Naoto Kawakami, Anneli Peters: T-B cell cooperation in ectopic lymphoid follicles propagates CNS autoimmunity. Science Immunology, 2025