John E. Butler, Ph.D.
Ph.D., University of Kansas, 1965 |
Professor of Microbiology Campus address: 3-550 BSB Mailing address: 51 Newton Rd. 3-550 Bowen Science Building Iowa City, IA 52242 Phone: 319-335-7776 Email: |
Antibody and T Cell Repertoire Development in Neonates
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.
Our recent and current research focuses on several aspects of this model system. First 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, which is required for development of adaptive immunity (1). Second, we are interested in the role of the ileal Peyers patches in this phenomenon and their role in B cell lymphogenesis, with special interest in IgG3 (2). Finally we are interested to know why certain variable region genes are predominately used during repertoire development (3).
The laboratory is also part of a Program Project that utilizes a piglet model for cystic fibrosis (CF). Transgenic pigs are used that have a disrupted gene encoding an ion channel transporter that is the hallmark of CF in humans. The laboratory is also involved in a second genetic engineering project that is developing B cell knockout pigs to make human antibodies.
Most recently we have characterized the antibody repertoire of bats, in the belief that an understanding of their immune system might help explain their loss from the ecosystem due to white-nosed syndrome which infects and kill hibernating bats.
References Cited
- Butler, J.E., D. Francis, J. Freeling, P. Weber, J. Sun, K.L. Nielsen, and A.M. Krieg. 2005. Antibody repertoire development in fetal and neonatal piglets. IX. Three PAMPs act synergistically to allow germfree piglets to respond to TI-2 and TD antigens. J. Immunol. 175:6772-6785.
- Butler, J.E., N. Wertz, N. Deschacht, and I. Kacskovics. 2009. Porcine IgG: Structure, genetics and evolution. Immunogenetics 61:209-230.
- Eguchi-Ogawa, T., N. Wertz, X.-Z. Sun, F. Puimi, H. Uenishi, K. Wells, P. Chardon, G.J. Tobin, and J.E. Butler. 2010. Anitbody repertoire development in fetal and neonatal piglets. XI. The relationship between variable heavy chain gene usage and the genomic organization of the variable heavy chain locus. J. Immunol. 184:3734-3742.