ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23

Weskamp, Gisela; Ford, Jill; Sturgill, Jamie; Martin, Steve L.; Docherty, Andrew; Swendeman, Steven; Broadway, Neil; Hartmann, Dieter; Säftig, Paul; Umland, Shelby P.; Sehara-Fujisawa, Atsuko; Black, Roy A.; Ludwig, Andreas; Becherer, J. David; Conrad, Daniel H.; Blobel, Carl P.

doi:10.1038/ni1399

Cited by 190 publications

(195 citation statements)

References 46 publications

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“…Incidentally, the present article also provides information on the development and maintenance of MZ B cells. First, two subsets of transitional B cells, termed T1 and T2, have been described (47 (48), it has been suggested that CD23 was lost at the MZ stage, probably due to its cleavage from the cell surface (49). A recent alternative interpretation is that the MZ-specific lineage never expresses CD23 and directly derives from T1 cells (50).…”

Section: Discussionmentioning

confidence: 99%

Critical Role of TLR2 and TLR4 in Autoantibody Production and Glomerulonephritis in lpr Mutation-Induced Mouse Lupus

Lartigue

Colliou²,

Calbo³

et al. 2009

The Journal of Immunology

133

100

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Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathogenic autoantibodies directed against nuclear Ags and immune complex deposits in damaged organs. Environmental factors have been thought to play a role in the onset of the disease. The recognition of these factors is mediated by TLRs, in particular TLR2 and TLR4 which bind pathogen-associated molecular patterns of Gram+ and Gram− bacteria, respectively. We attempted to determine the role of these TLRs in SLE by creating TLR2- or TLR4-deficient C57BL/6lpr/lpr mice. These mice developed a less severe disease and fewer immunological alterations. Indeed, in C57BL/6lpr/lpr-TLR2 or -TLR4-deficient mice, glomerular IgG deposits and mesangial cell proliferation were dramatically decreased and antinuclear, anti-dsDNA, and anti-cardiolipin autoantibody titers were significantly reduced. However, the response against nucleosome remained unaffected, indicating a role of TLR2 and TLR4 in the production of Abs directed against only certain categories of SLE-related autoantigens. Analysis of B cell phenotype showed a significant reduction of marginal zone B cells, particularly in C57BL/6lpr/lpr-TLR4-deficient mice, suggesting an important role of TLR4 in the sustained activation of these cells likely involved in autoantibody production. Interestingly, the lack of TLR4 also affected the production of cytokines involved in the development of lupus disease.

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Section: Discussionmentioning

confidence: 99%

Critical Role of TLR2 and TLR4 in Autoantibody Production and Glomerulonephritis in lpr Mutation-Induced Mouse Lupus

Lartigue

Colliou²,

Calbo³

et al. 2009

The Journal of Immunology

133

100

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“…We generated Taok3 antibody (directed against the stalk region of CD23) on day 0 and day2, by commercially available sCD23 ELISA (R&D systems), as described 10,30 . This 19G5 antibody causes ADAM10-dependent cleavage of sCD23.…”

Section: Methods Micementioning

confidence: 99%

“…This was not caused by altered Cd23 mRNA (data not shown). We have previously shown that the metalloproteinase ADAM10 determines the intensity of CD23 on the B cell plasma membrane, by cleaving CD23 to generate a sCD23 fragment 10,30 . We found that the baseline serum concentration of sCD23 was significantly reduced in Taok3 -/-mice compared with wild-type mice (Fig.…”

Section: Taok3 Controls the Surface Expression Of Adam10mentioning

confidence: 99%

Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10

et al. 2017

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2 Notch2 and B cell antigen receptor (BCR) signaling determine if transitional B cells become marginal zone B (MZB) or follicular B (FoB) cells in the spleen, but it isunknown how these pathways are related. We generated Taok3 equally important in B cell fate decisions [14][15][16] , and it was proposed that weak or strong BCR signals might render cells receptive or resistant to Notch instruction 17,18 . Yet how BCR repertoire or signaling controls Notch responsiveness is currently poorly understood.The Ste20 family kinases are serine-threonine kinases that participate in a variety of signaling pathways triggered by cellular stress 19,20 . The Tao kinase subfamily has three members in mammals (TAOK1, also known as proteins MAP3K16, PSK2 or MARKK; TAOK2 (MAP3K17, PSK1) and TAOK3 (MAP3K18, JIK or DPK)), whose function is largely unknown. Here, we generated Taok3 -/-mice and found that these mice lacked MZB cells, whereas FoB cells were intact. By carefully unraveling the molecular mechanism of this deficiency we have discovered how BCR signaling intersects with Notch signaling in immature transitional B cells undergoing positive selection. RESULTS 4 Taok3 -/-mice lack MZB cellsIn wild-type mice, the expression of mRNA for Taok3 was predominantly found in bone marrow and immune tissues like spleen, thymus and lymph nodes, but also in lung and gut (Fig. 1a). To gain insight into the biology of Taok3, we generated Taok3 -/-mice ( Supplementary Fig. 1a-e). Overall there was no difference in the cellularity of the various lymphoid organs in 6-12 week old mice (Supplementary Fig. 1f). In the spleen, there were no gross differences in the percentage of eosinophils, monocytes, natural killer (NK) cells and NKT cells between Taok3 -/-and wild-type mice, yet there was a consistent reduction in the amount of CD11c + dendritic cells in Taok3 -/-mice (Fig. 1b).There was a small yet consistent increase in the percentage of Ly6G + granulocytes in the spleen of Taok3 -/-mice. The distribution of CD3 + T cells and CD19 + B cells was comparable, yet there was a 25-30% reduction in the amount of CD8 + T cells (Fig. 1c). (Fig. 1d-f).Histological examination of the spleen revealed that the characteristic rim of IgM + CD1d + MZB cells separated from the IgM lo B cell follicles by the marginal sinus was absent in Taok3 -/-mice (Fig. 1g). Resident marginal zone metallophillic macrophages (MMM, expressing CD169) that line the marginal sinus were present and correctly localized in Taok3 -/-mice (Fig. 1h) (Fig. 1h). Collectively, Taok3 -/-mice lack MZB cells without compensatory alterations in other B cell subsets. Humoral immune response of Taok3 -/-miceThe baseline serum concentration of immunoglobulins (Ig) was comparable to wild-type, with a tendency for increased IgG3 in Taok3 -/-mice (Supplementary Fig 2) Fig. 1i and Supplementary Fig 2 ). The intact TNPspecific Ig response as not due to compensatory increase in recirculating MZB cells outside the spleen (data not shown). B1 B cells can also respond to TNP-Ficoll antigen, in the com...

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“…A single head domain binds to IgE-Fc with lower affinity (K A = 10 5 -10 6 M −1 ) than FcεRI (4)(5)(6)(7)(8), although avidity of the trimer can substantially enhance this interaction (7,(9)(10)(11). Membrane CD23 (mCD23) is cleaved from the cell surface by endogenous proteases such as ADAM10 (12,13) to yield soluble trimeric and monomeric forms (sCD23), which have been implicated in both positive and negative feedback mechanisms for the regulation of IgE synthesis by B cells that have switched to IgE production (1,7,8,(14)(15)(16). Both FcεRI and CD23 are also expressed on a range of antigenpresenting cells (APCs), where they play similar roles in trapping IgE-allergen complexes and promoting the allergic response (1,14,15), but the functional interplay-cooperation or competitionbetween these two receptors in the context of APCs is not well understood.…”

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confidence: 99%

Crystal structure of IgE bound to its B-cell receptor CD23 reveals a mechanism of reciprocal allosteric inhibition with high affinity receptor FcεRI

Dhaliwal

Yuan

Pang

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

136

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The role of IgE in allergic disease mechanisms is performed principally through its interactions with two receptors, FcεRI on mast cells and basophils, and CD23 (FcεRII) on B cells. The former mediates allergic hypersensitivity, the latter regulates IgE levels, and both receptors, also expressed on antigen-presenting cells, contribute to allergen uptake and presentation to the immune system. We have solved the crystal structure of the soluble lectin-like "head" domain of CD23 (derCD23) bound to a subfragment of IgE-Fc consisting of the dimer of Cε3 and Cε4 domains (Fcε3-4). One CD23 head binds to each heavy chain at the interface between the two domains, explaining the known 2:1 stoichiometry and suggesting mechanisms for crosslinking membrane-bound trimeric CD23 by IgE, or membrane IgE by soluble trimeric forms of CD23, both of which may contribute to the regulation of IgE synthesis by B cells. The two symmetrically located binding sites are distant from the single FcεRI binding site, which lies at the opposite ends of the Cε3 domains. Structural comparisons with both free IgE-Fc and its FcεRI complex reveal not only that the conformational changes in IgE-Fc required for CD23 binding are incompatible with FcεRI binding, but also that the converse is true. The two binding sites are allosterically linked. We demonstrate experimentally the reciprocal inhibition of CD23 and FcεRI binding in solution and suggest that the mutual exclusion of receptor binding allows IgE to function independently through its two receptors.antibody-receptor interactions | X-ray crystallography

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ADAM10 is a principal 'sheddase' of the low-affinity immunoglobulin E receptor CD23

Cited by 190 publications

References 46 publications

Critical Role of TLR2 and TLR4 in Autoantibody Production and Glomerulonephritis in lpr Mutation-Induced Mouse Lupus

Critical Role of TLR2 and TLR4 in Autoantibody Production and Glomerulonephritis in lpr Mutation-Induced Mouse Lupus

Transitional B cells commit to marginal zone B cell fate by Taok3-mediated surface expression of ADAM10

Crystal structure of IgE bound to its B-cell receptor CD23 reveals a mechanism of reciprocal allosteric inhibition with high affinity receptor FcεRI

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