Structures where the immune system recognizes antigens from the brain were found in the skull bone marrow of mice
Structures where the immune system recognizes antigens from the brain were found in the skull bone marrow of mice
On August 19, Nature published a study showing that these clusters of immune cells in mice responded to antigens originating in the brain. In a glioma model, suppressing the clusters weakened the antitumor immune response and reduced animal survival.
The brain is surrounded by cerebrospinal fluid, which bathes the brain and spinal cord. Channels connect the dura mater to the skull bone marrow, allowing cerebrospinal fluid and its dissolved substances to reach the adjacent tissue. A 2022 study traced this route and examined its effects on innate immune cells. The authors of the current study tested whether immune cells in the skull bone marrow could recognize antigens originating in the brain.
In the posterior skull bone marrow, the authors found clusters containing B cells that give rise to antibody-producing cells, helper T cells, and cells that present antigens to T cells. The B cells showed features of germinal centers, where B cells are selected and mature to produce antibodies. Comparisons with bone marrow from the sternum and femur, together with microscopy and single-cell analysis, showed that these clusters were particularly characteristic of the posterior skull bone marrow.
In another experiment, the researchers induced neurons in mice to produce a model protein antigen so that they could trace its route. They detected it in the cerebrospinal fluid, the membranes surrounding the brain, and the skull bone marrow. T and B cells that recognized the protein were activated in the same locations. The authors also introduced glioma cells carrying the same antigen either into the brain or under the skin on the flank of each mouse. A tumor inside the brain elicited a response in the skull bone marrow, whereas a tumor on the flank elicited a response in the inguinal lymph nodes. This control distinguished the response to brain-derived antigens from a general immune response to the tumor.
To test whether this response affected disease progression, the authors locally blocked CD40L, a signal through which T cells help B cells. In mice with glioma, this intervention reduced the activity of the structures in the skull bone marrow, immune cell infiltration into the tumor, and survival. A locally administered mixture of three immune stimulants strengthened the B-cell response in the skull and increased the activity of killer cells within the tumor, and the mice lived longer. This increase in survival depended on B cells and antibody-producing cells.
In mice, antigens from the brain reach the adjacent bone marrow and initiate a coordinated T-cell and B-cell response there. In a model of intracranial glioma, this response contributes to protection against the tumor.