Immune cells from skull bone marrow guard brain, spinal cord: study

2021-06-04 16:35:51 GMT2021-06-05 00:35:51(Beijing Time) Xinhua English

CHICAGO, June 4 (Xinhua) -- Two teams of researchers at Washington University School of Medicine in St. Louis unexpectedly found that many of the immune cells in the meninges come from bone marrow in the skull and migrate to the brain through special channels without passing through the blood, and these skull-derived immune cells are peacekeepers, dedicated to maintaining a healthy status quo.

Earlier this year, the researchers showed that immune cells stationed in the meninges keep tabs on the brain. Then the two teams independently launched projects to find where such cells come from, with one team focusing on the innate arm of the immune system and another on the adaptive arm.

Tracing the development of B cells, antibody-producing members of the adaptive immune system, the researchers found that most B cells in the meninges arose and matured in the skull bone marrow. As B cells mature, they must be taught to distinguish between normal proteins from the body, which pose no threat, and foreign proteins that signal infection or disease and require a response. For B cells destined for a life patrolling the boundaries of the central nervous system, the skull is a convenient site for this education.

"B cells in the bone marrow of the skull come into contact with the central nervous system and are educated by the central nervous system," said Marco Colonna, a professor of pathology. "That would not happen if they were released into the blood. Because they are directly in contact with the brain, they learn to be tolerant of brain proteins."

Along with the tolerant B cells derived from the skull, the researchers also discovered a population of B cells that come into the meninges from the blood. These blood-derived B cells are not trained to ignore normal central nervous system proteins. Some of these cells may wrongly recognize harmless central nervous system proteins as foreign and produce antibodies against them. Moreover, the number of these blood-derived B cells increases with age, providing a clue to why the risk of neuro-immune conditions is higher in older people.

Meanwhile, another team of researchers searched for the source of meningeal myeloid cells, a group of innate immune cells, and found that myeloid cells arose in the bone marrow of the skull and spinal vertebrae and entered the meninges via direct channels through the bone.

Using mouse models of multiple sclerosis and of brain and spinal cord injuries, the researchers found that myeloid cells swarm into the brain and spinal cord in response to injury or disease. Most of the entering cells are drawn from the resident population of myeloid cells in the meninges. These are biased toward regulating and modulating the immune response. But some myeloid cells come in from the blood, and these are more inflammatory, capable of causing damage if not properly controlled.

"Understanding where these cells come from and how they behave is a critical part of understanding the basic mechanisms of neuro-immune interactions, so we can design new therapeutic approaches for neurological conditions associated with inflammation," said Jonathan Kipnis, a professor of pathology and immunology. "The location of these cells in the skull makes them relatively accessible, and opens up the possibility of designing therapies to alter the behavior of these cells and treat neuro-immune conditions."

The study was published Thursday in the journal Science. Enditem

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