Cutting edge: Regulation of TLR4-driven B cell proliferation by RP105 is not B cell autonomous

Jessica L. Allen, Leah M. Flick, Senad Divanovic, Shaun W. Jackson, Richard J Bram, David J. Rawlings, Fred D. Finkelman, Christopher L. Karp

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Mechanistic understanding of RP105 has been confounded by the fact that this TLR homolog has appeared to have opposing, cell type-specific effects on TLR4 signaling. Although RP105 inhibits TLR4-driven signaling in cell lines and myeloid cells, impaired LPS-driven proliferation by B cells from RP105 -/- mice has suggested that RP105 facilitates TLR4 signaling in B cells. In this article, we show that modulation of B cell proliferation by RP105 is not a function of B cell-intrinsic expression of RP105, and identify a mechanistic role for dysregulated BAFF expression in the proliferative abnormalities of B cells from RP105 -/- mice: serum BAFF levels are elevated in RP105 -/- mice, and partial BAFF neutralization rescues aberrant B cell proliferative responses in such mice. These data indicate that RP105 does not have dichotomous effects on TLR4 signaling and emphasize the need for caution in interpreting the results of global genetic deletion.

Original languageEnglish (US)
Pages (from-to)2065-2069
Number of pages5
JournalJournal of Immunology
Volume188
Issue number5
DOIs
StatePublished - Mar 1 2012

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B-Lymphocytes
Cell Proliferation
Myeloid Cells
Cell Line
Serum

ASJC Scopus subject areas

  • Immunology

Cite this

Allen, J. L., Flick, L. M., Divanovic, S., Jackson, S. W., Bram, R. J., Rawlings, D. J., ... Karp, C. L. (2012). Cutting edge: Regulation of TLR4-driven B cell proliferation by RP105 is not B cell autonomous. Journal of Immunology, 188(5), 2065-2069. https://doi.org/10.4049/jimmunol.1103282

Cutting edge : Regulation of TLR4-driven B cell proliferation by RP105 is not B cell autonomous. / Allen, Jessica L.; Flick, Leah M.; Divanovic, Senad; Jackson, Shaun W.; Bram, Richard J; Rawlings, David J.; Finkelman, Fred D.; Karp, Christopher L.

In: Journal of Immunology, Vol. 188, No. 5, 01.03.2012, p. 2065-2069.

Research output: Contribution to journalArticle

Allen, JL, Flick, LM, Divanovic, S, Jackson, SW, Bram, RJ, Rawlings, DJ, Finkelman, FD & Karp, CL 2012, 'Cutting edge: Regulation of TLR4-driven B cell proliferation by RP105 is not B cell autonomous', Journal of Immunology, vol. 188, no. 5, pp. 2065-2069. https://doi.org/10.4049/jimmunol.1103282
Allen, Jessica L. ; Flick, Leah M. ; Divanovic, Senad ; Jackson, Shaun W. ; Bram, Richard J ; Rawlings, David J. ; Finkelman, Fred D. ; Karp, Christopher L. / Cutting edge : Regulation of TLR4-driven B cell proliferation by RP105 is not B cell autonomous. In: Journal of Immunology. 2012 ; Vol. 188, No. 5. pp. 2065-2069.
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