Enhanced B cell expansion, survival, and humoral responses by targeting death receptor 6

Clint S. Schmidt, Jinqi Liu, Tonghai Zhang, Ho Yeong Song, George Sandusky, Karen Mintze, Robert J. Benschop, Andrew Glasebrook, Derek D. Yang, Songqing Na

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Targeted disruption of death receptor (DR)6 results in enhanced CD4+ T cell expansion and T helper cell type 2 differentiation after stimulation. Similar to T cells, DR6 is expressed on resting B cells but is down-regulated upon activation. We examined DR6-/- B cell responses both in vitro and in vivo. In vitro, DR6-/-- B cells undergo increased proliferation in response to anti-immunoglobulin M, anti-CD40, and lipopolysaccharide. This hyperproliferative response was due, at least in part, to both increased cell division and reduced cell apoptosis when compared with wild-type B cells. Consistent with these observations, increased nuclear levels and activity of nuclear factor κB transcription factor, c-Rel, and elevated Bcl-x1 expression were observed in DR6-/- B cells upon stimulation. In addition, DR6-/- B cells exhibited higher surface levels of CD86 upon activation and were more effective as antigen-presenting cells in an allogeneic T cell proliferation response. DR6-/- mice exhibited enhanced germinal center formation and increased titers of immunoglobulins to T-dependent as well as T-independent type I and II antigens. This is the first demonstration of a regulatory role of DR6 in the activation and function of B cells.

Original languageEnglish (US)
Pages (from-to)51-62
Number of pages12
JournalJournal of Experimental Medicine
Volume197
Issue number1
DOIs
StatePublished - Jan 1 2003

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Keywords

  • Apoptosis
  • CD40
  • Hyperproliferation
  • Spleen
  • TNFR superfamily

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Schmidt, C. S., Liu, J., Zhang, T., Song, H. Y., Sandusky, G., Mintze, K., Benschop, R. J., Glasebrook, A., Yang, D. D., & Na, S. (2003). Enhanced B cell expansion, survival, and humoral responses by targeting death receptor 6. Journal of Experimental Medicine, 197(1), 51-62. https://doi.org/10.1084/jem.20020617