A research team led by Dr. Woong-Kyung Suh at the IRCM published on November 13th a paper in the Proceedings of the National Academy of Sciences (PNAS), a prestigious scientific journal from the USA. This work identified a crucial signal transduction mechanism that promotes the production of the key immunological weapon: antibodies. Mathieu Gigoux and Jijun Shang, a Master’s student and a technician at the IRCM, respectively, are the joint first co-authors of this paper.

Antibodies play pivotal roles in protecting our bodies from infectious agents such as viruses. A group of white blood cells called “B cells” become antibody producing cells during an immune reaction. To ensure that B cells produce high-quality antibodies against invaders but not against the body’s own cells or harmless environmental antigens, B cells should be guided by another type of white blood cells called “follicular B helper T cells” or Tfh.

Tfh cells arise from naïve precursor T cells upon antigenic challenges. It has been known that the generation of Tfh depends on a receptor on the T cell surface called “Inducible Costimulator (ICOS).” The importance of ICOS in antibody responses has been manifested in a group of patients with an inherited immunodeficiency syndrome. The patients have mutations in the ICOS gene that lead to defective generation of Tfh cells and antibodies. However, little has been known about how ICOS supports the generation of Tfh cells.

In the paper, Dr. Suh’s team definitively shows that ICOS activates an enzyme named “phosphoinositide 3-kinase (PI3K)” that in turn augments the production of the key soluble factors (cytokines) that facilitate the generation of Tfh cells. Thus, genetically engineered mice with a selective abrogation of ICOS-PI3K signaling axis show as dramatic defects as mice that do not have ICOS at all. This study identified PI3K as a key component that mediate ICOS function and provides a framework for future efforts to identify targets that could be manipulated to enhance or suppress antibody responses in various infectious or autoimmune diseases.

This study was supported by the Canadian Institutes of Health Research (CIHR).

This article is available online.

Dr. Woong-Kyung Suh is Director of the Immune Regulation Research Unit at the IRCM. He is Assistant Research Professor IRCM, Assistant Professor of the Department of Medicine at the Université de Montréal and Associate Member of the Department of Microbiology and Immunology and of the Division of Experimental Medicine at McGill University.

Communications Department