Study unveils how antibodies reach the blood
When we get infected by a virus or a bacterium, the conduit system inside lymph nodes is co-opted and converted from its usual function – getting information about the inflammation state of the organism – to rapidly transport antibodies outside the lymph nodes and into the blood stream. The discovery is reported this week in the Journal of Experimental Medicine by the research team led by Matteo Iannacone of IRCCS Ospedale San Raffaele, in collaboration with Marc Bajénoff’s lab at the Centre d’Immunologie de Marseille- Luminy in France. The novel mechanism, unveiled using advanced microscopy techniques, explains for the first time the efficiency and speed of the immune response against pathogens.
Antibodies play a fundamental role in targeting and neutralizing viruses and bacteria upon infections. They are produced by B cells inside lymph nodes, but in order to exert their protective function they must reach the blood circulation. Especially for the first wave of neutralizing antibodies – that provides immediate but low specificity defense before the production of high-affinity antibodies – timing is crucial: antibodies have to move quickly from the inner part of the lymph node to the periphery, at a rate hard to explain postulating a passive diffusion of the molecules through the organ, also because of their dimension and weight.
To solve the enigma, the researchers led by Matteo Iannacone looked at the three-dimensional network of reticular fibers known as the conduit system, an infrastructure crossing the lymph node from its inner part to the periphery. Besides their structural support function, usually these conduits serve as a transport system to move cytokines and other inflammatory signals from the outer regions to the center of the organ, thus collecting information about possible threats that require immune activation.
“We discovered that following the production of antibodies, the conduit system is co-opted and converted to perform a completely different job: exporting antibodies from the lymph nodes into the blood stream, from where they can reach the infected tissue”, says Matteo Iannacone. “Our results show a novel biological function for the conduit system, proving once more the key role of this structure in dealing rapidly and efficiently with pathogen infections and in orchestrating immunity upon vaccine administration”.
Guilhem R. Thierry, Mirela Kuka, Marco De Giovanni, Isabelle Mondor, Nicolas Brouilly, Matteo Iannacone, Marc Bajénoff, The conduit system exports locally secreted IgM from lymph nodes, Journal of Experimental Medicine, Nov 2018.