Abstract
Like many of us who had the great fortune to work with Bill Paul, my science life was immeasurably altered by my interactions with him. Although intimidating at first because of his stature in the immunology world, it was soon clear that he not only truly cared about the specific research we were doing together, but he wished to convey to his trainees an approach to science that was open, always questioning, and infinitely fun. His enthusiasm was infectious and after my training with him, despite stresses due to funding and publishing hurdles, I never regretted the path I took. My research took a sharp turn from the studies of adaptive immunity I had planned on pursuing after my fellowship with Bill to a life long quest to understand the wonders of the mast cell, a relatively rare innate immune cell. This came about because Bill’s curiosity and expectation of the unexpected allowed him to view, in retrospect, a rather mundane observation we made together involving a non-physiological transformed mast cell line as something that might be really interesting. I have never forgotten that lesson: Look at the data with an eye on the big picture. Sometimes the unexpected is more interesting than predicted results. His example in this regard was incredibly important when as an independent investigator a mistake in mouse sex determination led to unexpected and very confusing data. Yet, these data ultimately revealed a role for mast cells in male-specific protection in experimental autoimmune encephalomyelitis, the mouse model of multiple sclerosis. Bill’s influence in immunology is far-reaching and will continue to be felt as those of us who train our own students and post-doctoral fellows pass on his wisdom and approach to scientific research.
Highlights
In January of 1983, I arrived at the Laboratory of Immunology, NIAID, NIH, to work as a postdoctoral fellow with Bill Paul
Carboxypeptidase 3 (Cpa3)-Cre; Mcl-1fl/fl mice were generated by crossing Cpa3-Cre mice with mice containing a floxed Myeloid leukemia sequence 1 gene and exhibit a 92–100% reduction of mast cells in all sites tested with the exception of the spleen [20]
Mast cells are most often associated with blood vessels and nerves and are present in the brain, where they are most numerous in thalamus and hippocampus [23, 24]
Summary
In January of 1983, I arrived at the Laboratory of Immunology, NIAID, NIH, to work as a postdoctoral fellow with Bill Paul. Subsequent studies by Marshall Plaut, Robert Seder, and Achsah Keegan in Bill’s laboratory demonstrated that IL-4 production is induced in activated non-transformed lines after IgE receptor cross-linking, but that activated mast cells are a source of other cytokines, both in culture and in vivo [9,10,11]. They revealed that IL-3 priming significantly increases cytokine production by IgE-stimulated mast cells [12]. They are anemic, have neutrophilia, and show a dramatic reduction in basophils in the bone marrow and blood
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