Yet exactly how it helps formulate immune responses to serious and sometimes fatal infections like malaria and sepsis has remained somewhat of a mystery until now.
Enter Professor Scott Mueller and his team at the Peter Doherty Institute for Infection and Immunity, who - in a world first - have discovered a new gene that plays an important role in the way the spleen functions.
Their research has also uncovered multiple new cells within the enigmatic 200 gram organ which sits between the ninth and eleventh ribs, and revealed the distinct way they respond to fight off affliction.
Prof Mueller says as well as helping combat disease and infection, the spleen is also central to the body's immune response to vaccines.
However science has struggled to grasp precisely how it functions, something critical in helping develop new ways to boost immunity and improve disease outcomes.
The University of Melbourne academic says while scientists have known for some time that the spleen is made up of networks of cells called fibroblasts, a clear picture of how they are constructed and function was lacking.
"Using novel biological tools and next generation sequencing, we were able to examine precisely how specialised types of fibroblast cells dictate how the spleen works," he said.
"Along with identifying multiple new subtypes of fibroblasts, we discovered a new gene - SpiB - that plays an important role in guiding the development and function of these cells."
This new understanding may lead to new treatments for diseases such as severe acute virus infections and chronic infections.
"By surveying the fibroblast landscape of the spleen and providing the first in-depth look at the gene expression, we have been able to create detailed plans to the scaffold of this unique organ," Prof Mueller said.
"These plans can now be utilised to discover new targets to treat diseases involving the spleen, as well as enable the design of more efficient vaccines."
The Doherty Institute research findings have been published in Science Immunology.
