Gustav J. Nossal
University of Melbourne
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Primary Section: 43, Immunology and Inflammation Secondary Section: 41, Medical Genetics, Hematology, and Oncology Membership Type:
International Member
(elected 1979)
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Research Interests
My research centers on the cellular basis of antibody formation and of immunological tolerance. In 1957, Joshua Lederberg and I discovered that in immunizing an animal with two different antigens, individual cells from the draining lymph node make one antibody, not two. Later work proved that the lymphocytes from unimmunized animals were equally individually committed. Lymphocytes bear only one recognition unit on their surface as a receptor. The immune response involves the selection of that cell for division and differentiation. My interests also centered on the question of immunological memory. Gordon Ada and I discovered that certain spherical structures in lymphoid tissues, known as primary lymphoid follicles, had within them a special network of antigen-retaining cells, the follicular dendritic cells which were able to capture and hold the antigen on their surface, in an immunogenic form, for long period of time without endocytosis or processing. Around these follicular dendritic cells there developed a structure known as the germinal center, the site of somatic hypermutation which improved the quality of antibody as the immune response progressed. Immunological tolerance is the phenomenon whereby the body does not react to its own constituents. When this self-recognition breaks down, autoimmune disease may result. Working with those lymphocytes that are the precursors of antibody-forming cells, the so-called B lymphocytes, I discovered two key mechanisms of tolerance which we termed "clonal abortion" and "clonal anergy." These findings were later confirmed by others using sophisticated transgenic models. Finally, we discovered a novel mechanism of apoptosis in germinal centers which was a reflection of the fact that hypermutation must not be allowed to create cells with autoimmune potential.
