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

34 Citations (Scopus)

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 2003
Externally publishedYes

Fingerprint

Death Domain Receptors
Cell Survival
B-Lymphocytes
T-Lymphocytes
Germinal Center
Antigen-Presenting Cells
Cell Division
Immunoglobulin M
Lipopolysaccharides
Immunoglobulins
Cell Differentiation
Transcription Factors
Cell Proliferation
Apoptosis

Keywords

  • Apoptosis
  • CD40
  • Hyperproliferation
  • Spleen
  • TNFR superfamily

ASJC Scopus subject areas

  • Immunology

Cite this

Enhanced B cell expansion, survival, and humoral responses by targeting death receptor 6. / Schmidt, Clint S.; Liu, Jinqi; Zhang, Tonghai; Song, Ho Yeong; Sandusky, George; Mintze, Karen; Benschop, Robert J.; Glasebrook, Andrew; Yang, Derek D.; Na, Songqing.

In: Journal of Experimental Medicine, Vol. 197, No. 1, 01.2003, p. 51-62.

Research output: Contribution to journalArticle

Schmidt, CS, Liu, J, Zhang, T, Song, HY, Sandusky, G, Mintze, K, Benschop, RJ, Glasebrook, A, Yang, DD & Na, S 2003, 'Enhanced B cell expansion, survival, and humoral responses by targeting death receptor 6', Journal of Experimental Medicine, vol. 197, no. 1, pp. 51-62. https://doi.org/10.1084/jem.20020617
Schmidt, Clint S. ; Liu, Jinqi ; Zhang, Tonghai ; Song, Ho Yeong ; Sandusky, George ; Mintze, Karen ; Benschop, Robert J. ; Glasebrook, Andrew ; Yang, Derek D. ; Na, Songqing. / Enhanced B cell expansion, survival, and humoral responses by targeting death receptor 6. In: Journal of Experimental Medicine. 2003 ; Vol. 197, No. 1. pp. 51-62.
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