New regulator plays critical role in development B cells

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.