Dendritic cells are replenished from blood

Dendritic cells help direct the body’s immune response by presenting invading antigens to T cells so they know what to attack. But an ongoing debate exists about where dendritic cells originate and how they multiply, especially in the spleen and lymph system. Now, in a paper published in this month’s issue of Nature Immunology, Rockefeller University scientists have come a step closer to understanding the origins of the spleen and lymph node dendritic cells, findings that are especially important for researchers developing immune-cell-targeted vaccines.

Prior studies suggested that dendritic cells in the spleen either must continually divide and renew their population, or must be constantly replenished from precursor cells migrating from the bone marrow. Resolving the debate is important, says Kang Liu, postdoctoral associate and the study’s first author, because if dendritic cells divide endlessly then they could be acting as a reservoir for pathogens. “On the other hand, dividing could also allow them to present antigens to T cells for a longer period and prime the immune system to fight the pathogens off,” Liu says.

The study by Liu and Michel Nussenzweig, Sherman Fairchild Professor and head of the Laboratory of Molecular Immunology, appears to resolve the debate. According to their research, spleen and lymphoid dendritic cells migrate to these organs through the blood as “dendritic cell precursors,” mature into dendritic cells, divide a few times and then die, leaving a void to be replenished by bone marrow precursors.

By joining two mice together so that they shared the same bloodstream, a technique called parabiosis, the scientists found that even though the mice shared most of their immune cells equally, they only had about a 30 percent exchange rate in their spleen and lymph node dendritic cells. These dendritic cells were continually being replaced by precursors from the blood, precursors that were never evenly distributed between the two mice because they were removed from circulation too quickly to equilibrate.

Liu and Nussenzweig, who’s also an HHMI investigator, found three main factors for the maintenance of a mouse’s population of spleen and lymph node dendritic cells: continuous replenishment of dendritic cell precursors from the blood at a rate of about 4,300 cells per hour, the limited division of differentiated dendritic cells and the dendritic cell death rate. “These dendritic cells can’t last longer than 14 days without being replenished, and the number of dendritic cells can be the rate-limiting factor of immune response,” Liu says. “This is the first time that their division and self-renewal capacity has been directly measured.”