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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0803660v1 183/4/2585    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Jackson, L. Articles by Cambier, J. C. PubMed PubMed Citation Articles by Jackson, L. Articles by Cambier, J. C.

TLR4-Mediated Signaling Induces MMP9-Dependent Cleavage of B Cell Surface CD23¹

Department of Immunology, University of Colorado Denver School of Medicine and National Jewish Health, Denver, CO 80206

IgE production is inversely regulated by circulating and B cell surface levels of the low affinity IgE receptor, CD23. To begin to understand physiologic determinants of CD23 expression, we analyzed effects of BCR and TLR stimulation on CD23 levels. BCR and TLR 2, 3, 4, 6, and 9 agonists induced CD23 down-modulation from the cell surface. However, among the ligands only TLR4 agonists induced transcriptional activation of CD23 and generation of significant soluble CD23. These responses were induced by LPS both in vitro and in vivo, and were seen in both murine and human B cells. LPS also induced expression of matrix metalloprotease 9 (MMP9) and failed to induce CD23 cleaving activity in MMP9^–/– cells, thus implicating MMP9 in the LPS-induced release of CD23 from the cell surface. Finally, type 1 transitional B cells uniquely produce MMP9 in response to LPS, suggesting a mechanism wherein endotoxin induces T1 cell expression of MMP9, which mediates cleavage of CD23 on distinct, mature B cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported by grants from the U.S. National Institutes of Health. L.J.J. was supported in part by the Cancer Research Institute predoctoral emphasis pathway in tumor immunology fellowship. C.C. was supported by a fellowship from National Jewish Health.

² Current address: Array Bioharma, 3200 Walnut Street, Boulder, CO 80301.

³ Address correspondence and reprint requests to Dr. John C. Cambier, Department of Immunology, K803A, National Jewish Health, 1400 Jackson Street, Denver, CO 80206. E-mail address: CambierJ{at}njhealth.org

⁴ Abbreviations used in this paper: m, membrane bound; s, soluble; MMP, matrix metalloprotease; ADAM, A Disintegrin And Metalloprotease; qPCR, quantitative real-time PCR; FO, follicular; MZ, marginal zone.

⁵ The online version of this article contains supplemental material.