EphB2 contributes to human naive B‐cell activation and is regulated by miR‐185

Abstract

EphB2 is an important member of the receptor tyrosine kinases. Recently, EphB2 was shown to facilitate T-cell migration and monocyte activation. However, the effects of EphB2 on B cells remain unknown. In this study, the expression of EphB2 on B cells was tested by Western blot, and the roles of EphB2 in B-cell proliferation, cytokine secretion, and immunoglobulin (Ig) production were evaluated using EphB2 siRNA interference in human B cells from healthy volunteers. Our study revealed that EphB2 was distributed on naive B cells and was up-regulated on activated B cells. Moreover, B-cell proliferation (decreased by 22%, P<0.05), TNF-α secretion (decreased by 40%, P<0.01) and IgG production (decreased by 26%, P < 0.05) were depressed concordantly with the down-regulated EphB2 expression. Subsequently, we screened microRNAs that could regulate EphB2 expression in B cells, and discovered that miR-185 directly targeted to EphB2 mRNA and suppressed its expression. Furthermore, miR-185 overexpression inhibited B-cell activation, and the inhibitor of miR-185 enhanced B-cell activation. Moreover, abatement of EphB2 through miR-185 mimics or EphB2 siRNA attenuated the activation of Src-p65 and Notch1 signaling pathways in human B cells. Our study first suggested that EphB2 was involved in human naive B cell activation through Src-p65 and Notch1 signaling pathways and could be regulated by miR-185.

Exosomes, DAMPs and miRNA: Features of Stress Physiology and Immune Homeostasis

“…Some number of miRNA have been reported to modulate immune processes. Mir-26a-5p, mir-140-3p and mir-339-5p, for example, can inhibit NF-κB expression [42–44]; and mir-185-5p and mir-200a-3p can regulate immune cell proliferation and differentiation [45, 46]. While to role of miRNAs has largely been studies in cells, miRNAs can also readily be found in the blood.…”

MicroRNAs in the key events of systemic lupus erythematosus pathogenesis

“…The regulation of apoptosis during Gc B cells maturation is tightly regulated, the anti-apoptotic bcl-2 protein is down-regulated in Gc B cells and both Gc elevated mir-15a and mir-16 directly inhibit it 136 . mature B cells express mir-150 and mir-185, but expression of both is after activation reduced 131,137 . The mir-185 indirectly supports B cell activation such as production of igG and TNF-α cytokine while negatively regulate the ephB2 expression 137 .…”

“…mature B cells express mir-150 and mir-185, but expression of both is after activation reduced 131,137 . The mir-185 indirectly supports B cell activation such as production of igG and TNF-α cytokine while negatively regulate the ephB2 expression 137 . on contrary, mir-210 is induced after B cell activation 130 .…”

Identification of microRNAs implicated in the late differentiation stages of normal B cells suggests a central role for miRNA targets ZEB1 and TP53

“…A very interesting observation is related to miR-185 expression pattern: published results, in fact, demonstrated that this miRNA was upregulated in mouse GC B cells and downregulated in human GC B cells after stimulation of naïve B cells with lipopolysaccharide antigen [21, 35]. MiR-185 is able to switch off the BTK kinase, that plays a critical role in controlling the positive and negative selection of autoreactive B cells in mice [36], by influencing the B cell receptor signaling pathway [21].…”