Finding immune cells under our noses

The nose is a major gateway to our bodies, from the air we breathe, to the scents we smell, to the microbes we may inhale. Have you ever wondered about the mechanics of how your body fights off a head cold or why nasal vaccines work? It’s not as straightforward as it seems: because the nose is close to the brain, it is therefore largely off-limits to antibodies. But the olfactory system is not defenseless. In fact, it has its own way of fighting back.

As recently detailed in Nature, Prof. Ziv Shulman and his team in the Department of Systems Immunology revealed that antibody-producing cells migrate from lymph nodes into the nasal tissue and start producing antibodies on site when we are infected or vaccinated. This discovery could pave the way for more effective nasal vaccinations and new treatments for nervous system disorders, allergies, and autoimmune diseases.

Jingjing Liu, a PhD student in the Shulman lab, used advanced imaging techniques to examine how immune system organs near the nose and throat respond to nasal vaccinations. She found that in mice—whose near-nose immune system is similar to humans—a nasal vaccination triggers a response from B cells, the body’s main antibody-producing immune cells. B cells are first “schooled” in recognizing the specific vaccine antigen, then migrate into tiny immune cell “training camps” within the nasal lymph nodes. Here, they interact with T cells to select and produce the best-suited antibodies to match the vaccine.

T cells play a crucial role in immune defense, but their presence is limited in the area near the nose, due to its proximity to the brain. This is actually beneficial, as having too many T cells in this area could prompt oversensitivity to harmless quantities of airborne particles, triggering allergies.

To clarify this process further, Prof. Shulman and Liu zeroed in on the cellular products of the nasal lymph nodes. Once a fully trained set of B cells has finally been prepared, the key into the mucus-producing glands of the nose’s bone tissue, where they now secrete their antibodies. This finding was surprising because this specific bone niche was not previously known to get involved in vaccine-induced immune responses. But secreting antibodies right there, on-site, rather than in typical immune niches, helps B cells achieve their goal—and what they lack in numbers, they make up for in localization at the pathogen invasion site. Moreover, this local secretion of antibodies also helps protect the brain and olfactory nerves.

In addition to facilitating vaccine design, Prof. Shulman notes that this research has exposed “an entry point into a highly fortified target—antibody-secreting cells that have access to the central nervous system.” In the future, it may be possible to use the antibody-secreting cells’ access to the olfactory nerves to design vaccines for neurological diseases.

Prof. Ziv Shulman is supported by the Moross Integrated Cancer Center and Rising Tide Foundation.