The Knight Lab has three major areas of research: 1) The role of intestinal microflora in the development of gut-associated lymphoid tissues (GALT) and the primary antibody repertoire, 2) The mechanism by which B cell development in bone marrow arrests, and 3) Rapid restoration of immune competence in cancer patients treated with hematopoietic stem cells from umbilical cord blood. Projects 1 and 2 utilize rabbits, and project 3 utilizes a SCID mouse model. 

Rabbit studies:  

Rabbits are members of the so-called GALT (gut-associated lymphoid tissues) species, in which B cells develop in bone marrow early in ontogeny and then migrate to GALT where they greatly expand in number and somatically diversify their immunoglobulin (Ig) genes, leading to generation of the primary antibody repertoire. B cell expansion, somatic diversification of Ig genes, and selective expansion of particular subsets of B cells in GALT requires the presence of intestinal microbiota (Rhee et al. 2004). One major focus of our laboratory is to study the mechanism by which intestinal bacteria promote these processes. These studies include identification of host and/or bacterial molecules that stimulate B cells in GALT following exposure to intestinal microbiota (Kari Roettger); cytokines and cell-cell interactions required for B cell expansion in GALT (Venkata Yeramilli) and identification and characterization of bacterial mutants that do not promote GALT development and somatic diversification of Ig genes (Periannan Sethupathi, and Kari Roettger). Dr. Dennis Lanning, Research Assistant Professor, has developed in situ hybridization techniques to analyze how bacterial colonization of GALT affects expression of chemokines and cytokines that attract B cells during GALT development and promote B cell proliferation.

Another major focus of our laboratory is B cell development in the bone marrow. We found that B cells are generated in bone marrow of rabbits for only the first few weeks of life (Jasper et al, 2003), even though lymphopoietic stem cells are found throughout the rabbit's life (Susan Kalis et al, 2007). We use in vitro and in vivo techniques to determine the molecular and cellular mechanisms by which B cell development is arrested in young rabbits (Fareena Bilwani). We recently identified a new isoform of IL-7 that contains an 11 amino acid insertion and we are determining if this isoform contributes to the arrest of B lymphopoiesis in adult rabbits (Mae Kingzette and Basile Siewe). We are also investigating how B cell immunity is maintained in adults in the absence of on-going B lymphopoiesis (Pi-Chen Yam and Greg Robbins).

Another project in our laboratory is to develop methods to rapidly restore a competent immune system in adult cancer patients treated with hematopoietic stem cells from umbilical cord blood (Britte Beaudette and Shi-Kang Zhai).  We culture cord blood hematopoietic stem cells in vitro to expand B and T cell progenitors and then test the capacity of these cells to develop a normal human immune system following injection into NODSCIDIL2Rg-/- mice

We invite you to explore our site further and find out more about these projects (People and Projects). We have also included some of our laboratory protocols for your use, especially that for developing rabbit monoclonal antibodies.