John Owen conducted pioneering work on lymphocyte development in the vertebrate immune system. By using cell marker techniques, he showed that T and B cells derive from stem cells that migrate into the embryonic thymus and avian bursa of Fabricius, respectively. In addition, he demonstrated the importance of stem cell migration during the development of the blood system.

He showed that B cells are initially produced in the mouse foetal liver, thereby identifying blood-forming tissues in mammals as the equivalent of the bursa of Fabricius — the main site of B cell development in birds.

By micromanipulating single thymus stem cells into explants of thymus epithelium, he and his colleagues demonstrated that major subclasses of T cells, as well as T-cell receptor diversity, can derive from a common precursor cell. By the use of embryonic thymus lobes in tissue culture, he showed that major histocompatibility complex (MHC) antigens expressed on thymus stromal cells are responsible for removal of self-reacting T cells by apoptosis (activated cell suicide), thus contributing to immunological tolerance to ‘self’.