An important breakthrough by IRCM researchers in hematopoiesis and the
development of B cells

MONTREAL, Dec. 22 /CNW Telbec/ - A team at the Institut de recherches cliniques de Montréal (IRCM) led by Dr. Tarik Möröy, President and Scientific Director of the institute and Director of the Hematopoiesis and Cancer research unit, will be publishing an important breakthrough in tomorrow's issue of Immunity, a scientific journal from the Cell Press group. The researchers identified a new regulator playing a critical role in the development B cells, which produce antibodies.

Antibodies circulate through the blood and protect against infectious diseases originating from bacteria or viruses. A lack of antibodies causes the immune system to be severely compromised against infections, and is therefore life-threatening. By producing specific antibodies, mature functional B cells are essential for the body's immune response. The regulator discovered by the researchers is a transcription factor called Miz-1, which is needed for the proper development and maturation of B cells in the bone marrow. This maturation process also requires a growth factor called Interleukin-7 (IL-7) that enables the development of B cells by providing it with the necessary survival signals.

"We initially wanted to clarify the role of Miz-1 during hematopoiesis, which is the formation of all blood cellular components," explains Dr. Christian Kosan, Research Associate in Dr. Möröy's research unit and the study's first author. "Surprisingly, our study demonstrated that Miz-1 is required predominantly for the very early stages of B-cell development in the bone marrow. For instance, after deleting the Miz-1 gene in a mouse, we discovered that it had almost completely lost its ability to generate B cells. "

Upon closer evaluation, the research team found that Miz-1 has a very particular function: it is required for IL-7 to effectively trigger the maturation of B cells in the bone marrow. For that reason, mice lacking the Miz-1 transcription factor were immunocompromised, and with this severe defect in B-cell production, a pathogen invasion would most certainly lead to rapid death.

"The important breakthrough in this study is the discovery that the IL-7 signaling pathway uses the transcription factor Miz-1 to ensure both B-cell survival and maturation," adds Dr. Möröy. "Our research project therefore confirmed the importance of this signaling pathway for the development of antibody-producing cells. Our next step will be to study the impact of Miz-1 in the development of B-cell leukemia. If this regulator is necessary for the production of B cells, it is possible that it is also required for the development of B-cell leukemia. It may thus be a target for therapeutic interventions in the treatment of this type of blood cancer."

Ingrid Saba, a graduate student in the IRCM's Hematopoiesis and Cancer research unit, is the second author of the study. This research project was conducted in collaboration with Dr. Martin Eilers, professor at the University of Würzburg (Germany), and his team. The study was supported by a grant from the Canadian Institutes of Health Research (CIHR) and the Canada Research Chair (Tier 1) held by Dr. Möröy.

For more information, please refer to the article summary published by Immunity: http://www.cell.com/immunity/abstract/S1074-7613(10)00458-9.

About Dr. Tarik Möröy
Tarik Möröy obtained his PhD in biochemistry from the Ludwig-Maximilians University in Munich, Germany. He is President and Scientific Director of the IRCM, Full IRCM Research Professor and Director of the institute's Hematopoiesis and Cancer research unit. Dr. Möröy is also Full Research Professor in the Department of Microbiology and Immunology, as well as an accredited member in the Department of Biochemistry at the Université de Montréal. In addition, he is Adjunct Professor in the Department of Biochemistry and associate member of the Division of Experimental Medicine at McGill University. Dr. Möröy holds a Tier-1 Canada Research Chair in Hematopoiesis and Immune Cell Differentiation.

About the Institut de recherches cliniques de Montréal (IRCM)
Founded in 1967, the IRCM (www.ircm.qc.ca) is currently comprised of 37 research units in various fields, namely immunity and viral infections, cardiovascular and metabolic diseases, cancer, neurobiology and development, systems biology and medicinal chemistry, and clinical research. It also houses three specialized research clinics, as well as eight core facilities and two research platforms with state-of-the-art equipment. The IRCM employs 450 people and is an independent institution affiliated with the Université de Montréal. The IRCM clinic is associated to the Centre hospitalier de l'Université de Montréal (CHUM). The IRCM also maintains a long-standing association with McGill University.

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