Abstract
Mice deficient in the NF-κB transcription factor relB appear to have defects in the production of mature dendritic cells, as secondary lymphoid tissues are absent, and spleen cells show a significant loss of antigen presenting function. Moreover, the thymus appears to be impaired in negative selection, and immune responses in vivo are poor. Since dendritic cell precursors such as skin Langerhans cells appear to be normal, we sought information on the nature of the dendritic cell defect in these mice. Cultures of mutant bone marrow in the presence of GM-CSF revealed a delay in the accumulation of cells with dendritic cell features relative to controls; however, these cells were nearly as potent on a per cell basis as wild type cells in the stimulation of allogeneic mixed lymphocyte cultures. Similarly, skin Langerhans cells from mutant mice also showed significant ability to stimulate allogeneic T cells in culture. Since these findings cannot explain the defect in immune responses and the absence of secondary lymphoid tissues, we also looked at the ability of the relB mutant dendritic-like cells to form aggregates in vitro with naive syngeneic T cells. In this case, while wild type dendritic cells generated compact aggregates with T cells, relB mutant cells only formed irregular small aggregates. Thus, while relB mutant dendritic-like cells have some functions of mature dendritic cells, other functions are deficient. Understanding the role of relB in regulation of these functions should lead to a greater understanding of the molecular basis of dendritic cell development and function.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ryseck, R.P., Bull, P., Takamiya, M., Bours, V., Siebenlist, U., Dobrzanski, R, and Bravo, R., RelB, a new Real family transcription activator that can interact with p50-NF-KB. Mol. Cell. Biol. 12: 674–684, 1992.
Lo, D., Quill, H., Burkly, L., Scott, B., Palmiter, R.D., and Brinster, R.L., A recessive defect in lymphocyte and/or granulocyte function caused by an integrated transgene. Am. J. Pathol., 141: 1237–1246, 1992.
Burkly, L., Hession, C., Ogata, L., Reilly, C., Marconi, L.A., Olson, D., Tizard, R., Cate, R., and Lo, D., Expression of relB is required for the development of thymic medulla and dendritic cells. Nature 373: 531–536, 1995.
Weih, F., Carrasco, D., Durham, S.K., Barton, D.S., Rizzo, C.A., Ryseck, R.-P., Lira, S.A., and Bravo, R., Multiorgan inflammation and hematopoietic abnormalities in mice with a targeted disruption of relB, a member of the NF-KB/Rel family. Cell 80: 331–340, 1995.
Laufer, T.M., DeKoning, J., Markowitz, J.S., Lo, D., Glimcher, L.H., Unopposed positive selection and autoreactivity in mice expressing class II MHC only on thymic cortex. Nature 382: 81–85, 1996.
DeKoning, J., DiMolfetto, L., Reilly, C., Wei, Q., Havran, W., Lo, D., T cell development in relB deficient mice: Positive selection and acquisition of function do not require thymic medulla. Submitted, 1996.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Science+Business Media New York
About this chapter
Cite this chapter
Dimolfetto, L., Reilly, C., Wei, Q., Lo, D. (1997). Dendritic-Like Cells from relB Mutant Mice. In: Ricciardi-Castagnoli, P. (eds) Dendritic Cells in Fundamental and Clinical Immunology. Advances in Experimental Medicine and Biology, vol 417. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9966-8_8
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9966-8_8
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9968-2
Online ISBN: 978-1-4757-9966-8
eBook Packages: Springer Book Archive