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Myosin Family Protein Regulates Immunity

Dr. Gupta and her team have uncovered a novel role for the protein Myo18A in restricting B cell antibody responses, indicating that this protein controls adaptive immunity


Recent findings published by Department of Inflammation & Immunity researchers in The Journal of Immunology have defined how the protein Myo18A acts as a brake on antibody-mediated immunity. The investigators—led by Neetu Gupta, PhD, who directs the Center of Excellence in Lymphoid Malignancies Research—are the first to examine the function of Myo18A in B lymphocytes of the adaptive immune system, importantly finding that the protein controls the earliest stages of B cell development, as well as anti-viral immunity.

Dr. Gupta and her colleagues began researching Myo18A almost a decade ago, while investigating novel binding partners of another cytoskeletal protein, Ezrin. That initial study, published in the Journal of Proteome Research, provided the first clue that Myo18A may have a regulatory role in B cell immunity.

“We were intrigued by Myo18A because of its potential to interact with specific proteins that control cellular architecture and molecular transport across various cellular compartments,” said Dr. Gupta.

B cells and antibody responses

The researchers used gene editing technologies to delete Myo18A from B cells and then examined the effects of the deficiency at different phases during B cell development and maturation.

“We found that the loss of Myo18A enhanced B cell development in the bone marrow, lymph nodes, and spleen,” said Dr. Gupta. “Myo18A-deficiency was also associated with higher levels of circulating antibodies. Further, Myo18A-deficient mice mounted a stronger neutralizing antibody response against the H1N1 strain of Influenza A virus. Taken together, these finding suggest that normal Myo18A levels hamper antibody-mediated immunity.”

Next steps to explore mechanisms

Ongoing studies in the lab will use a multi-pronged approach that aims to identify the molecular and cellular basis for the regulatory role of Myo18A in B cells. The team will identify the molecular mechanisms that enable Myo18A to control B cell development, differentiation and antibody production. Another interesting aim of these studies is using next generation sequencing and characterize neutralizing antibodies that are generated in the absence of Myo18A. The fundamental insights gained from these approaches are expected to provide a framework for better understanding of B cell-mediated immunity, and have implications in the design of vaccines against flu and other existing and emerging pathogens

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