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RESEARCH HIGHLIGHTS

Nature Reviews Immunology | Published online 30 May 2017; doi:10.1038/nri.2017.62

fascinated by the idea that the anti-B alloantiserum plus complement Journal club thymus might function as an would abolish antibody formation endocrine organ that I later turned up by spleen cells in vitro in a plaque- T CELL–B CELL COLLABORATION in Miller’s laboratory asking to do a forming cell (PFC) assay. The clear-cut Ph.D. on thymic hormones. finding was that only anti-A antiserum The field of T cell immunology began I was soon brought up-to-date on ablated PFC formation. in 1961 with a landmark paper by the recent work of Miller’s graduate This simple yet elegant approach Jacques Miller demonstrating the student, Graham Mitchell, who was proved that thymus-dependent effects of neonatal thymectomy (NTx) investigating the notable observation antibody production reflected an in mice, which included a marked of Claman et al. in 1966 that, in interaction between thymus-derived paucity of lymphocytes, signs of irradiated hosts, antibody responses to and bone marrow-derived cells (T and infection (hepatitis) and, remarkably, sheep red blood cells (SRCs) required B cells, respectively), an observation failure to reject allogeneic and even both thymocytes and bone marrow that changed the face of immunology xenogeneic (rat) skin grafts. These thymus- cells. The key unresolved issue was — and convinced me to forget about findings evoked intense interest and dependent which of these cell types made thymic hormones! were soon extended by several other antibody. It should be noted that Jonathan Sprent groups. However, it was a 1968 paper antibody Mitchell only had crude alloantisera Garvan Institute, Sydney, from Miller’s group that first showed production specific for two mouse strains (A and New South Wales 2010, Australia. [email protected] that the thymus is a direct source of B) at his disposal. However, this was reflected an The author declares no competing interests. T helper cells for antibody production. interaction enough. Modifying the approach of Although the early studies of NTx Claman et al., Mitchell and Miller ORIGINAL ARTICLE Mitchell, G. F. & Miller, J. F. proved that the thymus controls between developed a model in which anti-SRC Cell to cell interaction in the immune response. II. cellular immunity, it remained thymus- responses were generated in adult The source of hemolysin-forming cells in irradiated mice given bone marrow and thymus or thoracic possible that, rather than arising in derived and thymectomized, irradiated (A × B) F1 duct lymphocytes. J. Exp. Med. 128, 821–837 (1968) the thymus per se, immunocompetent mice that were injected with a mixture FURTHER READING Miller, J. F. Immunological cells were generated elsewhere by bone marrow- of strain A bone marrow cells and function of the thymus. Lancet 2, 748–749 (1961) | Claman, H. N., Chaperon, E. A. & Triplett, R. F. ‘hormones’ released from the thymus. derived cells F1 thymocytes or thoracic duct Thymus–marrow cell combinations. Synergism in As a medical student, I heard Miller lymphocytes plus SRCs. A week antibody production. Proc. Soc. Exp. Biol. Med. 122, lecture in the mid‑1960s and was so later, they tested whether anti-A or 1167–1171 (1966)