Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide

Nagai, Yoshinori; Shimazu, Rintaro; Ogata, Hirotaka; Akashi, Shigeo; Sudo, Katsuko; Yamasaki, Hidetoshi; Hayashi, S.; Iwakura, Yoichiro; Kimoto, Masao; Miyake, Kensuke

doi:10.1182/blood.v99.5.1699

Cited by 162 publications

(147 citation statements)

References 30 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…However, murine TLR expression patterns differ from those in humans. Although it is well established that murine B cells respond to the TLR4 ligand LPS (48,49), in the present study and in our earlier studies (7,18) TLR4 expression in human B cells was found to be weak, and human B cells were not responsive to LPS with and without type I IFN priming. It is interesting to note that neither TLR2 nor TLR4 or TLR6 ligands were able to induce considerable polyclonal proliferation of human B cells, although all of them were strong inducers of TNF-␣ production in PBMC most likely due to monocyte activation.…”

Section: Discussionmentioning

confidence: 45%

Plasmacytoid Dendritic Cells Control TLR7 Sensitivity of Naive B Cells via Type I IFN

Berkeredjian-Ding

Wagner

Hornung

et al. 2005

The Journal of Immunology

299

215

View full text Add to dashboard Cite

Detailed information of human B cell activation via TLR may lead to a better understanding of B cell involvement in autoimmunity and malignancy. In this study we identified a fundamental difference in the regulation of TLR7- and TLR9-mediated B cell stimulation: whereas the induction of polyclonal naive B cell proliferation by the TLR7 ligands resiquimod (R848) and loxoribine required the presence of plasmacytoid dendritic cells (PDCs), activation via the TLR9 ligand CpG was independent of PDCs. We found that PDC-derived type I IFN enhanced TLR7 sensitivity of B cells by selectively up-regulating TLR7 expression. In contrast the expression levels of TLR9 and of other TLRs studied remained unchanged. In the presence of type I IFN, TLR7 ligation triggered polyclonal B cell expansion and B cell differentiation toward Ig-producing plasma cells; notably, this occurred independently of T cell help and B cell Ag. Human B cells did not respond to ligands of other TLRs including TLR2, TLR4 and TLR6 with and without type I IFN. In conclusion, our results reveal a distinct regulation of TLR7 and TLR9 function in human B cells and highlight TLR7 and TLR9 as unique targets for therapeutic intervention in B cell-mediated immunity and disease.

show abstract

Section: Discussionmentioning

confidence: 45%

Plasmacytoid Dendritic Cells Control TLR7 Sensitivity of Naive B Cells via Type I IFN

Berkeredjian-Ding

Wagner

Hornung

et al. 2005

The Journal of Immunology

299

215

View full text Add to dashboard Cite

show abstract

“…Miyake's group reported an association between myeloid differentiation protein 2 (MD2) with TLR4 which was required for TLR4-mediated LPS-signaling (Wakabayashi et al 2006). MD2 is an extracellular adaptor protein, associates with the extracellular domain of TLR4 and is indispensable for LPS recognition by TLR4 (Nagai et al 2002;Schromm et al 2001;Miyake et al 2000;Vabulas et al 2002). The binding of exogenous (e.g.…”

mentioning

confidence: 99%

PPARγ ameliorated LPS induced inflammation of HEK cell line expressing both human Toll-like receptor 4 (TLR4) and MD2

et al. 2015

View full text Add to dashboard Cite

TLR4 is transmembrane pattern-recognition receptor that initiates signals in response to diverse pathogen-associated molecular patterns especially LPS. Recently, there have been an increasing number of studies about the role of TLRs in the pathogenesis of several disorders as well as the therapeutic potential of TLR intervention in such diseases. Peroxisome proliferator-activated receptorgamma (PPARc) is a ligand-activated transcription factor with numerous biological effects. PPARc has been shown to exert a potential anti-inflammatory effect through suppression of TLR4-mediated inflammation. Therefore, PPARc agonists may have a potential to combat inflammatory conditions in pathologic states. The current study aims to show the decrease of inflammation by overexpression of PPARc in a cell reporter model. To reach this goal, recombinant pBudCE4.1 (?) containing encoding sequences of human TLR4 and MD2 was constructed and used to transfect HEK cells. Subsequently, inflammation was induced by LPS treatment as control group. In the treatment group, overexpression of PPARc prior to inflammation was performed and the expression of inflammatory markers was assessed in this condition. The expression of inflammatory markers (TNFa and iNOS) was defined by quantitative real time PCR and the amount of phosphorylated NF-jB was measured by western blot. Data indicated expression of TNFa and iNOS increased in LPS induced inflammation of stably transformed HEK cells with MD2 and TLR4. In this cell reporter model overexpression of PPARc dramatically prevented LPSinduced inflammation through the blocking of TLR4/ NF-jB signaling. PPARc was shown to negatively regulate TLR4 activity and therefore exerts its antiinflammatory action against LPS induced inflammation.

show abstract

“…Radioprotective 105 (RP105) forms a complex with MD-1 and can transmit powerful survival as well as proliferation signals when cross-linked by Abs (12)(13)(14). RP105 Ϫ/Ϫ or MD-1 Ϫ/Ϫ mice, like animals deficient in TLR4 or MD-2, are hyporesponsive to LPS (15,16), but precise mechanisms that functionally couple the two types of complex remain unclear.…”

mentioning

confidence: 99%

The Radioprotective 105/MD-1 Complex Links TLR2 and TLR4/MD-2 in Antibody Response to Microbial Membranes

Nagai¹,

Kobayashi²,

Motoi³

et al. 2005

The Journal of Immunology

Self Cite

116

View full text Add to dashboard Cite

Low-affinity IgG3 Abs to microbial membranes are important for primary immune defense against microbes, but little is known about the importance of TLRs in their production. IgG3 levels were extremely low in mice lacking radioprotective 105 (RP105), a B cell surface molecule structurally related to TLRs. RP105−/− B cells proliferated poorly in response to not only the TLR4 ligand LPS but also TLR2 ligand lipoproteins, both of which mediate the immunostimulatory activity of microbial membranes. RP105−/− mice were severely impaired in hapten-specific Ab production against LPS or lipoproteins. CD138 (syndecan-1)-positive plasma cells were detected after lipid A injection in wild-type spleen but much less in RP105−/− spleen. RP105 ligation in vivo induced plasma cell differentiation. RP105 expression was ∼3-fold higher on marginal zone B cells than on follicular and B1 cells and was down-regulated on germinal center cells. These results demonstrate that a signal via RP105 is uniquely important for regulating TLR-dependent Ab production to microbial membranes.

show abstract

Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide

Cited by 162 publications

References 30 publications

Plasmacytoid Dendritic Cells Control TLR7 Sensitivity of Naive B Cells via Type I IFN

Plasmacytoid Dendritic Cells Control TLR7 Sensitivity of Naive B Cells via Type I IFN

PPARγ ameliorated LPS induced inflammation of HEK cell line expressing both human Toll-like receptor 4 (TLR4) and MD2

The Radioprotective 105/MD-1 Complex Links TLR2 and TLR4/MD-2 in Antibody Response to Microbial Membranes

Contact Info

Product

Resources

About