TLR stimulation modifies BLyS receptor expression in follicular and marginal zone B cells

Laura S. Treml, Gianluca Carlesso, Kristen L. Hoek, Jason E. Stadanlick, Taku Kambayashi, Richard J. Bram, Michael P. Cancro, Wasif N. Khan

Research output: Contribution to journalArticlepeer-review

116 Scopus citations


Through their differential interactions with B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), the three BLyS family receptors play central roles in B cell survival and differentiation. Recent evidence indicates BLyS receptor levels shift following BCR ligation, suggesting that activation cues can alter overall BLyS receptor profiles and thus ligand sensitivity. In this study, we show that TLR stimuli also alter BLyS receptor expression, but in contrast to BCR ligation, TLR9 and TLR4 signals, preferentially increase transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI) expression. Although both of these TLRs act through MyD88-dependent mechanisms to increase TACI expression, they differ in terms of their downstream mediators and the B cell subset affected. Surprisingly, only TLR4 relies on c-Rel and p50 to augment TACI expression, whereas TLR9 does not. Furthermore, although all follicular and marginal zone B cells up-regulate TACI in response to TLR9 stimulation, only marginal zone B cells and a subset of follicular B cells respond to TLR4. Finally, we find that both BLyS and APRIL enhance viability among quiescent and BCR-stimulated B cells. However, although BLyS enhances viability among TLR stimulated B cells, APRIL does not, suggesting that TACI but not BLyS receptor 3 may share survival promoting pathways with TLRs.

Original languageEnglish (US)
Pages (from-to)7531-7539
Number of pages9
JournalJournal of Immunology
Issue number12
StatePublished - Jun 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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