Molecule CD20 is crucial for the interaction between T and B cells Role of target for first-ever antibody cancer therapy finally clarified

The very first antibody therapy ever developed against cancer was directed against CD20, a molecule found on B cells of our immune system. However, the function of CD20 in the body remained unclear for a long time. Researchers led by Radboud University Medical Center have now shown that CD20 is crucial when B cells activate the immune response via T cells.

Back in 1997, researchers developed antibodies that bind to CD20, a molecule that is specifically found on B cells in our immune system. This antibody therapy is effective against B cell tumors, and also against autoimmune diseases in which B cells play a key role, such as rheumatoid arthritis and multiple sclerosis. But the actual biological role of CD20 was not known.

Researchers led by Annemiek van Spriel, Professor of Experimental Immunology at the department of Medical Biosciences at Radboudumc, have now changed that. They show that CD20 is essential for proper communication between B cells and T cells in the immune system. Without CD20, a specific immune response by T cells is insufficiently activated.

Presentation

When a B cell detects a pathogen, it presents parts of that pathogen to a T cell. This activates the T cell, which then eliminates the pathogen. During this presentation, the B cell and T cell briefly stick tightly together. ‘The area where the cells make contact is called a synapse, and we now show that CD20 is crucial for the formation of this synapse’, says Van Spriel.

Without CD20, B cells cannot properly attach to T cells. In addition, the researchers showed that the T cells are not activated to clear the danger. They were able to measure this by analyzing the T cells themselves and the substances these cells produce when they are activated.

Van Spriel and her colleagues used not only cell lines and blood cells from healthy volunteers for their research, but also cells from a patient with a mutation in the gene for CD20. This patient was unable to produce CD20 and suffered from frequent infections. In the lab, it turned out that her B and T cells barely made contact, and thus the T cells did not become active.

Clusters

Finally, the researchers extensively mapped the organization of CD20 on the surface of cells. Van Spriel: ‘CD20 forms clusters of twenty to forty molecules that are highly mobile and move across the cell membrane as a group. A single B cell contains about 20,000 of these CD20 molecules on average.’

All this new knowledge advances the research field. Van Spriel: ‘Although antibody therapy against CD20 is successful, about forty percent of patients with aggressive B cell cancer unfortunately do not respond to it. If we understand more about how this molecule works and is organized, we may be able to overcome therapy resistance and improve new immune therapies targeting CD20.’

A B cell (green) binds to a T cell (blue) to present parts of a pathogen. CD20 proves to be crucial for this connection between the two cell types.

About the publication

This research has been published in PNAS: CD70 recruitment to the immunological synapse is dependent on CD20 in B cells. Abbey B. Arp, Andrea Abel Gutierrez, Martin ter Beest, +20, Annemiek B. van Spriel. DOI: 10.1073/pnas.2414002122.

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