2023-07-12 06:00:04
A team from the Montreal Clinical Research Institute (IRCM), led by Dr. Javier Di Noia, Director of the B Cell Molecular Biology Research Unit at the IRCM and Full Research Professor at the University of Montreal (The University of Montreal is one of four teaching institutions…), recently discovered a mechanism that underlies the generation of effective immune responses, an advance that has great potential for application in therapies against lymphoma (a lymphoma is a lymphatic cancer, ie a cancer of the lymphatic system with…).
The research team’s findings, published in the Journal of Experimental Medicine, show that an enzyme called PRMT1 plays a key role in triggering high-quality antibody responses, a crucial aspect in prevention (Prevention is an attitude and/or the set of measures to be taken to avoid…) infectious diseases.
B lymphocytes, known as B cells, the body’s guardians
B cells or B lymphocytes are an essential part of the immune system. As protective agents, their role is to produce antibodies responsible for fighting pathogens and any other form of threat that enter the body.
To develop their ability to recognize and effectively eliminate these threats, B cells work to improve the quality of their antibodies. This is a kind of formative period during which the B lymphocyte prepares to produce better antibodies before it can fight the infection effectively. To do this, B cells must differentiate into specialized cells called plasma cells, the body’s defense squad that makes large amounts of antibodies, or into memory cells, a reserve army ready for action later.
The example of vaccination
The basic process of antibody immune responses has been known for years in the medical field. In fact, it is the basis of vaccination, which has made it possible to overcome many deadly infectious diseases such as measles (Measles (also called 1st disease) is an eruptive viral infection…), rubella (Rubella (or 3rd disease) is an epidemic viral disease, of neighboring incubation…) and smallpox, among others. Vaccination allows the body to come into contact with a germ rendered harmless. The B cells are thus brought into contact with the germ and have the possibility of producing corresponding high-quality antibodies. They then become either plasma cells which secrete protective antibodies, or memory B lymphocytes (In general, memory is the storage of information. It is also memory…). In vaccinated individuals, memory B cells are a discreet but effective army of sentinels circulating in the blood to detect early any future exposure to the same pathogen (The term pathogen (from the Greek παθογ?νεια!… ) and which prevents the infection from developing.
However, questions remain about the underlying mechanisms that regulate the formation of efficient plasma cells and memory cells. In particular, the one by which B lymphocytes work to improve antibody quality or differentiate into plasma or memory cells is critical. Early differentiation would result in low quality antibodies, while too late differentiation could lead to fatal infection. The question of the fate of B cells is also important for B cell cancers, called lymphomas, because they then grow in an uncontrolled way avoiding differentiation.
“We are interested in these questions because a deeper knowledge of such molecular mechanisms is essential to direct research towards more precise and more effective therapeutic options”, explains Dr Di Noia, who is also an assistant professor at the McGill University (McGill University, located in Montreal, Quebec, is one of…).
A study that sheds new light
Dr. Di Noia’s study showed that an enzyme called PRMT1 could provide answers to some of these questions.
First, PRMT1 plays an important role in the quality of the immune response. When this enzyme is absent or weak, differentiation occurs too quickly, not allowing the process to be optimal. This is because B cells that differentiate too early produce poor quality plasma and memory cells, which in turn will produce less effective antibodies and ineffective memory, thus compromising the success of the immune response.
Thus, the PRMT1 acts as a gatekeeper to the decision-making process. It regulates the appropriate rhythm defining the ideal time for the differentiation of B lymphocytes, which gives them time to improve their antibodies. This increases the effectiveness of antibodies in the bloodstream (Bloodstream is a type of closed-circuit circulatory system that ensures…), allows the triggering of high-quality memory responses, and results in a stronger and more immune response. effective.
“This knowledge helps us better understand the conditions for effective vaccination and what happens when it does not work well,” says Dr Di Noia.
Second, the PRMT1 enzyme also acts in the growth of cancerous B cells that cause lymphomas. Lymphoma develops when the system malfunctions, causing B cells to proliferate indefinitely, preventing them from differentiating or dying. The IRCM team discovered that PRMT1 is highly expressed in certain human biological samples of lymphomas and that high expression of the enzyme in B-cell lymphomas is associated with a poor prognosis.
Specifically, the team demonstrated that an excess of the PRMT1 enzyme stimulates the proliferation of cancerous B cells, thereby contributing to disease progression. This excess also prevents differentiation, which nevertheless has a suppressive effect on tumours.
Encouraging prospects
This important work suggests that manipulation of the PRMT1 enzyme could hold promise for optimizing the immune response and opening the door to new solutions to combat lymphoma. The discovery of the critical role of PRMT1 in the immune response also raises other possibilities, in particular that mutations of the enzyme could be the cause of certain immunodeficiencies.
“This central role of PRMT1 in immune cells opens up a promising new avenue of research, as it encourages further research on this enzyme and other proteins of the same family, mentions Dr. Di Noia. Our study also contributes to justify the development of PRMT1 inhibitors for the fight against cancer.”
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