Dennis Lanning, PhD
Research Assistant Professor
Ph.D., Ohio State University
Major Research Interests: Bacterial stimulation of GALT development.
The initial antibody repertoire produced by neonatal rabbits is of limited diversity due to restricted use of V, D and J gene segments during V(D)J recombination. Rabbit B cells generate a highly diversified primary, or preimmune, antibody repertoire by somatically mutating their V(D)J genes in gut-associated lymphoid tissue (GALT) between 3 and 6 weeks of age. Both rabbit GALT development and antibody repertoire diversification are dependent on select members of the intestinal microbiota. Our laboratory is interested in understanding the nature of the host-microbial interactions that drive these developmental processes. We are currently investigating whether select intestinal bacteria drive chemokine-mediated positive feedback interactions between B cells and stromal cells that have been found to be crucial for secondary lymphoid tissue organogenesis in mice. We study the impact of intestinal bacteria on chemokine expression in GALT by using immunohistochemistry and in situ hybridization, as well as by interrupting chemokine-mediated interactions with chemokine receptor-Ig fusion proteins introduced via an adenovirus system. Our results suggest that select intestinal bacteria drive chemokine-mediated positive feedback interactions between B cells and stromal cells by inducing B cell proliferation, and we are beginning to focus on the mechanism of bacterially-induced B cell proliferation in rabbit GALT.
Hanson, N. B. and D. K. Lanning (2008). Microbial induction of B and T cell areas in rabbit appendix. Dev. Comp. Immunol. 32(8):980-91.
Lanning, D. K., Severson, K. M. and K. L. Knight (2008). Intestinal Bacteria: Mucosal Tissue Development and Gut Homeostasis. In: Immunity Against Mucosal Pathogens. (M. J. Vajdy, ed.) (in press).
Lanning D. K., Rhee K.-J. and K. L. Knight (2005). Intestinal Bacteria and Development of the B lymphocyte Repertoire. Trends in Immunology 26: 419-425.
Esteves, P. A., Lanning, D., Ferrand, N., Knight, K. L., Zhai, S.-K., and W. van der Loo (2005). The evolution of the immunoglobulin heavy chain variable region (IgVH) in Leporids: an unusual case of trans-species polymorphism Immunogenetics 57: 874-882.
Lanning, D., Osborne, B. A. and K. L. Knight (2004). Immunoglobulin Genes and Generation of Antibody Repertoires in Higher Vertebrates: A Key Role for GALT. In: Molecular Biology of B cells. (F. W. Alt, T. Honjo and M. S. Neuberger, eds.), pp. 433-448, Elsevier Science Ltd.
Rhee, K.-J., Sethupathi, P., Driks, A., Lanning, D. K., and K. L. Knight (2004). Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire. J. Immunol. 172: 1118-1124.
Lanning, D., Zhai, S.-K. and K. L. Knight (2003). Analysis of the 3' Cµ region of the rabbit Ig heavy chain locus. Gene 309: 135-144.
Lanning, D., Sethupathi, P., Rhee, K.-J., Zhai, S.-K., and K. L. Knight (2000). Intestinal microflora and diversification of the rabbit antibody repertoire. J. Immunol. 165: 2012-2019.