Molecular Switch For Long-term Immunity Found

A protein responsible for preserving the antibody-producing cells that lead to long-term immunity after infection or vaccination has been
identified by researchers in Australia.

Presence of the protein Myb is essential for antibody-producing plasma cells to migrate into bone marrow, preserving them for many years or even decades, Dr Kim Good-Jacobson, Professor David Tarlinton and colleagues from the Walter and Eliza Hall Institute discovered.

Plasma cells, Dr Good-Jacobson said, are created when the immune system is exposed to pathogens such as viruses or bacteria:

“When our immune system encounters a new pathogen, it can create plasma cells that secrete antibodies to specifically prevent future infections, generating immunity.

Our bone marrow is like a long-term storage facility for plasma cells, allowing them to continue producing antibodies to protect against future infections. Until now, it was not known why some plasma cells moved into the bone marrow, while others remained in the blood stream and perished after a few days.”

Transcription Factor Protein

The research team found that when the gene that produces the protein Myb was removed, plasma cells were no longer able to move into the bone marrow to provide long-term immunity. Dr Good-Jacobson esplians:

“Myb is a type of protein called a transcription factor, which binds to DNA and, in effect, switches genes ‘on’ or ‘off’.

We found that if a plasma cell produced Myb at some stage during an immune response, then those plasma cells had the ability to migrate into the bone marrow. If we can understand how to flip the molecular switch in plasma cells and activate Myb production, we might be able to encourage the immune system to create long-term immunity for a range of infections.”

Creating Long-term Immunity

Plasma cells are created during an immune response in temporary structures called germinal centres, Dr Good-Jacobson said:

“Germinal centres act as a rapid proto-typing facility, improving the design of antibodies to better recognise invading pathogens in the future. The Myb protein marks the plasma cells that produce high-quality antibodies for preservation.”

Professor Tarlinton said the discovery would mean researchers could now search for the trigger of Myb production and find out what genes Myb controls.

“Now that we know Myb is critical in creating long-term immunity, we can begin dissecting the pathways it uses to mark plasma cells for storage and the genes involved in migrating to the bone marrow,” he said. “Some pathogens, such as malaria, typically trigger the creation of short-lived plasma cells. If we don’t create long-lived plasma cells, we don’t develop lasting immunity to the disease.

If we can trigger the expression of Myb in plasma cells responding to pathogens – either by infection or by immunisation – we might be able to convince the immune system to store these plasma cells in the bone marrow to offer protection against future infections.”

Reference:

Kim L. Good-Jacobson, Kristy O’Donnell, Gabrielle T. Belz, Stephen L. Nutt, and David M. Tarlinton
c-Myb is required for plasma cell migration to bone marrow after immunization or infection
JEM vol. 212 no. 7 1001-1009 doi: 10.1084/jem.20150191

Illustration: Julian Ma, Wellcome Images, Creative Commons by-nc-nd 4.0