Researchers have now identified a mechanism that may explain why some people have a higher risk of developing lymphoma

The immune system is designed to protect us against viruses and bacteria. 

In people with autoimmune diseases, the immune system instead attacks the body’s own cells. 

Conditions such as lupus and rheumatoid arthritis are well-known examples. It is estimated that just under 250,000 Norwegians live with some form of autoimmune disease. Approximately 8 to 10 per cent of the global population is affected.

“Researchers have long known that people with autoimmune diseases are more likely to develop lymphoma,” says Ramakrishna Prabhu Gopalakrishnan.

He is a researcher at the University of Oslo and Oslo University Hospital.

“But it has been unclear what actually links these diseases at the molecular level,” he says.

A finely tuned collaboration

In a new study, he and his colleagues have identified a possible mechanism that could help explain this connection. 

B cells and T cells are important parts of our immune system and work together to fight infections.

B cells produce antibodies that recognise and bind to foreign substances such as viruses and bacteria. 

T cells help coordinate the immune response. They can either support or dampen the activity of other immune cells.

Normally, this collaboration is carefully regulated.

When the immune system never switches off

In the new study, the researchers found that when the collaboration between B cells and T cells can sometimes become too strong and poorly regulated.

The cells then begin to activate each other continuously.

“At first, this leads to autoimmune disease. Over time, this prolonged and abnormal activation can also contribute to the development of lymphoma,” says Bjarne Bogen.

He is a professor and researcher at the University of Oslo and Oslo University Hospital.

The discovery could have implications for how lymphoma is treated in the future.

“The study is an important step towards understanding how our immune system, which normally protects us, can in some cases also contribute to cancer,” says Bogen.

Two signals that drive the disease forward

To better understand the significance of the findings, it may be useful to look more closely at what the researchers actually discovered. 

They investigated how the collaboration between B and T cells becomes chronic using a mouse model.

The researchers identified two crucial signals – messages that immune cells send to one another.

The first signal occurs when B cells mistakenly recognise the body’s own molecules as if they were foreign and dangerous. They then become partially activated.

For full activation, the B cell requires a second signal.

This second signal occurs when T cells recognise a specific part of the B cell’s own antibody structure. The T cells then amplify the activation that the B cells have already started.

“When these signals act together, a persistent and self-reinforcing cycle can develop, in which B and T cells can keep each other active,” explains Gopalakrishnan.

When control mechanisms fail

Normally, this mutual activation is controlled by regulatory T cells – a subset of T cells that ensure the immune response does not become excessive or harmful.

But sometimes this control mechanism fails. The body then loses control over the mutual activation between B and T cells. 

This leads to an abnormal and uncontrolled interaction and chronic overstimulation.

Such prolonged activation of immune cells can cause autoimmunity and thus contribute to the development of autoimmune diseases.

From defence mechanism to cancer risk

At the same time, this chronic overstimulation also increases the risk of genetic errors. 

When cells are constantly active and dividing, there is a greater chance of harmful genetic changes. Over time, this can cause both B cells and T cells to become cancerous.

The same immune reaction that starts as an autoimmune disease can, over time, lay the groundwork for cancer development, Gopalakrishnan points out.

“Our findings suggest that long-lasting and abnormal collaboration between specific immune cells may be a key driving force behind the development of lymphoma,” he says.

Important for future treatment

Several epidemiological studies have previously shown that patients with autoimmune diseases have an increased risk of developing non-Hodgkin B-cell lymphoma, a common type of lymphoma.

This new study now provides a biological explanation for that association.

By clarifying how lymphoma can develop at the molecular and cellular level, the researchers hope their findings will eventually contribute to better prevention and treatment strategies.

“In principle, this knowledge could make it possible to disrupt the harmful immune activation that occurs early in disease development,” says Bogen. “If we can intervene at the right time, it may be possible to reduce cancer risk in patients with autoimmune diseases, to develop more targeted treatments for lymphoma, and perhaps even to halt disease progression before cancer arises.”

Reference:

Gopalakrishnan et al. Idiotype-specific CD4+ T cells chronically stimulate autoreactive B cells to develop into B lymphomas in mice, Nature Communications, 2026. DOI: 10.1038/s41467-026-69916-w

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