NEW STUDY. The thymus gland plays a key role for our early immune system because this is where immune cells mature into specific T cells. A new study within inflammation and pediatrics research suggests that B cells in the thymus can help T cells learn to discriminate between endogenous and foreign structures in order to not cause autoimmune reactions.
The thymus is a gland located high in the chest cavity. Because it plays its most important role in the development of the early immune system, the thymus is larger during childhood. In the thymus, which acts as a sort of school for the T cells, the cells develop the receptors that allow them to recognize specific pathogens. Now researchers at Sahlgrenska Academy, along with colleagues at Italy’s Sapienza University of Rome, are highlighting another cell type also found in the thymus: B cells, which researchers previously did not know what their function was in the gland. The results were recently published in the Journal of Allergy and Clinical Immunology.
Samples from children with congenital heart disease
Through collaboration with Queen Silvia Children’s Hospital, the research team has gained access to unique tissue samples from human thymus glands.
“The thymus tissue has been removed from infants who have undergone heart surgery, allowing us to isolate and study B cells in the human thymus. We have also had access to blood samples from the same children who have donated thymus tissue, which allowed us to compare the B cells in the thymus and in blood,” says Christina Lundqvist, a doctoral student in the Department of Rheumatology and Inflammation Research and a lead author of the article, which will be included in her upcoming dissertation.
Few, but significant
The study shows that B cells represent a very small fraction of the total amount of cells in the thymus at only 0.3 percent. These B cells differ in many ways from the B cells found in the blood of the same children who donated thymus tissue.
“About half of B cells in the thymus lack a special marker called CD21 on their surface, which turned out to be more unusual in cells in the blood, where only 10 percent of B cells lack the marker,” says Alessandro Camponeschi, a postdoctor at the Department of Rheumatology and Inflammation Research who also was a lead author of the article. “We previously could see that B cells that lack the marker are more common in people with autoimmune diseases.”
The study points to several other differences between B cells in the thymus and in the blood.
“B cells in the thymus are often ‘class switched,’ which means they have been activated via their receptor, something we essentially do not see at all in the blood of newborn children. They also express a transcription factor called AIRE and have different activation markers on their surface, which we also do not see in B cells in the blood,” says Olov Ekwall, professor of pediatric immunology and co-author of the article.
Interact with and activate T cells in the thymus
As T cells mature in the thymus, an important selection takes place in which T cells that do not work as they should are eliminated. T cells that cannot distinguish endogenous from foreign substances, and thus can cause autoimmune diseases, also disappear. Based on the properties of the cells and the place in the thymus where the cells appear, the researchers assume that B cells present endogenous structures to T cells in the thymus.
“This is confirmed by the fact that in cell cultures or functional in vitro experiments, we saw that B-cells in the thymus had the ability to interact with and activate T cells when these types of cells are cultured together,” says Inga-Lill Mårtensson, also a co-author and professor of molecular medicine, especially basal illness mechanisms in cancer research and hematology.
The researchers will now proceed with additional studies to investigate the role of B cells in the thymus regarding tolerance development and autoimmune diseases.
TITLE: Switched CD21–/low B cells with an antigen-presenting phenotype in the infant thymus
AUTHORS: Christina Lundqvist, Alessandro Camponeschi, Marcella Visentini, Esbjörn Telemo, Olov Ekwall and Inga-Lill Mårtensson.
JOURNAL: Journal of Allergy and Clinical Immunology
TEXT: ELIN LINDSTRÖM CLAESSEN