Bill Ford: Manchester’s first Professor of Immunology
Bill Ford, Professor of Immunology
Those who know or worked with Bill Ford immediately recognised a man of enormous talent, humility and insight whose scientific work was imaginative, totally reliable and highly regarded. His appointment in 1975 to the chair of Experimental Pathology, later to become the chair in the new Department of Immunology, was timely for the University of Manchester. Bill was recognised internationally for his seminal investigations on lymphocyte recirculation and his appointment established Manchester as a centre of in vivo cellular immunology. His premature death from a road accident November 1984 was a tragic loss for science, medicine and especially for the University of Manchester. The University was about to embark on a major revolution to enhance biological research and teaching for which Bill Ford was earmarked to play a central role. Fortunately, he had already sown the seeds that helped to catapult Biological Sciences, later to become Life Sciences, into a centre of excellence.
Contributions to Manchester University
Bill was not just a renowned scientist, but also a gifted teacher. In Manchester he revolutionised Immunology teaching for medical and dental students, developing a core lecture programme underpinned by small group tutorials for all students. He established a popular BSc (Honours) course enabling medical students to acquire hands-on experience of fundamental research. He initiated a weekly Immunology seminar series and established the Manchester Immunology Group, a forum for inviting eminent speakers. Both seminar series continue to this day. Bill worked hard to forge new links between the Facilities of Medicine and Science – an initiative that led, after his death, to Manchester’s first undergraduate degree course in Immunology.
Contributions to knowledge
Born in Inverness in 1936, graduating MB, ChB with honours in medicine from Edinburgh University, and the recipient of a first class MA in physiology from Oxford, Bill, under the influence of Sir James Gowans, developed a passion for research. His experimental work established the foundations of knowledge that we now take for granted. Many of these studies were undertaken with numerous colleagues at a time before the discovery of monoclonal antibodies or flow cytometry and before there was any evidence for adhesion molecules or chemokines. Only a small sample of Bill Ford’s original observations (over 100 published papers) will be mentioned here.
Bill wanted to know how it was that lymphocytes alone – not granulocytes, not macrophages, not red blood cells – could escape the confines of the blood vasculature. Experimentally Bill and his group targeted unique vessels in LNs that were lined by “plump” endothelial cells – so called high endothelial venules (HEVs). Using radiolabelled lymphocytes and autoradiography they showed that lymphocytes injected into the blood stream rapidly adhered to the walls of HEVs. By 15 min lymphocytes had already escaped out of blood vessels and were present within LN tissue (see figure below). On entering LNs (and spleen) Bill and colleagues also demonstrated that both B and T lymphocytes immediately migrated in different directions to congregate in separate B- and T-cell compartments.
Postcapillary venule in paracortex of popliteal lymph node 15 min after the iv injection of [3H]-leucine-labeled B-thoracid duct lymphocytes. X40 oil immersion obj. Taken from Nieuwenhuis and Ford, Cell Immunol 23 254-267 (1976)
Puzzled by how lymphocytes might escape from the blood stream, Bill, with canny insight, imagined that lymphocytes might express unique molecules with an affinity for complementary molecules on the cells lining HEVs. Why he opted to inject radioactive sulphate is not clear, but Bill discovered that this radioisotope selectively labelled HEVs. Pursuing this clue, a PhD student (Paul Andrews*) was able to successfully isolate a sulphated glycoprotein from LNs that, much to their delight, blocked lymphocyte binding to HEVs. We now know that this sulphated molecule (Gly-CAM-1) is produced by high endothelial cells, binds with a receptor (L-selectin) on lymphocytes and initiates the first stages in the migration process. The hypothesis that Bill proposed was proved correct.
[* Tragically Paul and Bill died in the same road accident in Australia.]
Because the frequency of lymphocytes specific for any particular antigen is extremely low (1/10,000 to 1/ 1million), it was hypothesised that lymphocytes were constantly on the move in search of antigen. Bill and others showed that indeed this was the case. In addition, Bill’s group demonstrated that the tiny population of specific lymphocytes became rapidly trapped by antigen and concentrated within LNs and spleen. The specific cells were held in situ for several days allowing proliferation to occur before being released back into the blood stream. These observations provided concrete evidence that helped to establish the validity of Burnett’s clonal selection theory.
Bill also had a keen interest in transplantation. His work contributed significantly to our understanding of graft-versus-host disease during which transplanted lymphocytes attack the recipient. This disease is often a fatal complication of bone marrow transplantation. Bill’s group was also among the first to show that the frequency of T cells capable of attacking foreign tissue transplants, in complete contrast with the low frequency of common antigens, was astonishingly high (1-4%).
Bill set an example that was an inspiration to all who were lucky enough to have worked with him. He also laid the foundations that have allowed immunological research in Manchester to prosper and for the University to become a centre that attracts scientists from around the world.
Eric B Bell
Reader in Immunology
Friend and colleague