John Butler, PhD

Professor Emeritus of Microbiology and Immunology


photo of John Butler

Research Description

The antibody and T cell repertoires are somatically generated by combinatorial joining of variable region gene segments mediated by special recombinases. This generates a broad and sometime autoreactive pre-immune antibody repertoire, e.g. the innate natural antibody repertoire. This immature repertoire is refined and diversified by somatic hypermutation and selection to fashion an adaptive immune response/system. Refinement also involves changes in the class or subclass of antibodies used, e.g. IgG, IgA, etc. Four extrinsic factors; diet, maternal regulatory factors, gut flora and pathogens, impact the development of the adaptive immune system during a narrow window of neonatal life. Understanding how these factors promote the transition to adaptive immunity is important in human and animal health. Our studies utilize the isolator piglet model in which all four of theses extrinsic factors can be controlled by the experimenter. Of particular interest is the role played by colonizing gut flora, including probiotics, on repertoire development. Colonizing bacteria and some viruses are recognized by innate immune receptors, e.g. TLRs, and are required for development of adaptive immunity. In particular we continue to be interested in the role of the ileal Peyers patches which we have proposed to act as “first responder” mucosal immune tissue. As emeritus professor I will continue to advise and collaborate with other laboratories to pursue these studies. I will also continue to advise genetic engineering projects for developing B cell knockout pigs to make human antibodies and to prepare chimeric-camelid antibodies for species in which purified immunoglobulins can only produced in vitro.

I will also continue to advise projects on the immune system of bats in the belief that understanding their immune system might help explain the loss of insectivorous bats from the ecosystem due to white-nosed syndrome and how bats are vectors for human viruses but with rare exception (rabies) are not themselves victims of these diseases.