TLR4-Mediated Signaling Induces MMP9-Dependent Cleavage of B Cell Surface CD23

Abstract

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.

Aminoacyl tRNA Synthetase–Interacting Multifunctional Protein 1 Acts as a Novel B Cell–Activating Factor In Vitro and In Vivo

“…It is also known that CD23 is cleaved into a soluble form during cultivation (23). ADAM10 and MMP9 mediate the cleavage of surface CD23, and the loss of CD23 on the cell surface is observed during B cell culture (23,24). Therefore, knockdown of CD23 via RNA interference is also not suitable because the expression of surface CD23 is also decreased in the control groups.…”

“…However, it was difficult to find evidence to support our hypothesis because treatment with anti-CD23 blocking Abs activated B cells (22), which made it impossible to demonstrate inhibition of AIMP1-induced B cell activation. It is also known that CD23 is cleaved into a soluble form during cultivation (23). ADAM10 and MMP9 mediate the cleavage of surface CD23, and the loss of CD23 on the cell surface is observed during B cell culture (23,24).…”

Effect of IGHV Gene Mutation Status and BCR Structure Stereotypy on Effectiveness of BR Regimen in First-Line Therapy of Chronic Lymphocytic Leukemia

“…Можно предположить, что снижение экспрессии CD23 в стереотипных случаях является отражением повышенной активации лейкозных клеток. Так, по-давление экспрессии CD23 в В-лимфоцитах описано in vitro при активации Toll-подобных рецепторов и BCR [20,21]. При анализе БСВ в подгруппах пациентов с на-личием и отсутствием признаков соматической гипермутации IGHV-генов при использовании стан-дартного порога отсечения 2 % были выявлены ста-тистически значимые различия.…”

Antigen-specific Immunotherapy Regulates B Cell Activities in the Intestine

“…Previous reports indicate that activated B cells produce MMP9 that cleaves CD23 on the surface of B cells (13). To see whether the exposure to higher doses of SAV also increased the expression of MMP9 by B cells, we assessed the expression of MMP9 in the BCs.…”

“…How the specific antigens interact with immune cells to result in clinical outcomes is not fully understood yet. Because B cells express both CD23 and BCR (8,9,13), the antigens may interact with B cells to regulate B cell activities directly besides via the antigeninduced T cell activation and further influence the ongoing allergic diseases. Here we report that after exposure to specific antigens, a triple immune complex, antigen-IgE-CD23, was formed on the surface of BCs; the BCs then produced IL-10 and showed immune suppressor activities on skewed Th2 responses.…”