Scaffold protein JLP is critical for CD40 signaling in B lymphocytes [Immunology]

January 13th, 2015 by Wang, H.-m., Yan, Q., Yang, T., Cheng, H., Du, J., Yoshioka, K., Kung, S. K. P., Ding, G.-h.

The CD40 expression on the surface of B lymphocytes is essential for their biological function and fate decision. The engagement of CD40 with its cognate ligand, CD154, leads to a sequence of cellular events in B lymphocytes, which includes CD40 cytoplasmic translocation, a temporal and spatial organization of effector molecules and a cascade of CD40-induced signal transduction. The JLP scaffolding protein was expressed in murine B lymphocytes. Using B lymphocytes from the jlp-deficient mice, we observed that the JLP deficiency resulted in defective CD40 internalization upon CD154/CD40 engagement. Examination of interactions and co-localization among CD40, JLP, dynein, and Rab5 in B lymphocytes suggested that CD40 internalization is a process of JLP-mediated vesicle transportation that depends on Rab5 and dynein. JLP deficiency diminished also CD40-dependent activation of MAPK and JNK, but not NF-κB. Inhibiting vesicle transportation from cell peripheral to cell center by a dynein inhibitor ciliobrevin D impaired both the CD154-induced CD40 internalization and CD40-dependent MAPKs activities in B lymphocytes. Collectively, our data demonstrated a novel role of the JLP scaffolding protein in the bridging of CD154-triggered CD40 internalization and CD40-dependent signaling in splenic B lymphocytes.