Researchers identify new regulator that play a critical role in B cell development

A team at the Institut de recherches cliniques de Montr-al (IRCM) led by Dr. Tarik M-r-y, 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. M-r-y'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. M-r-y. "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."

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