Down-regulation of CD20 on B cells upon CD40 activation

✍ Scribed by Jennifer Anolik; R. John Looney; Andrea Bottaro; Iñaki Sanz; Fay Young

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 566 KB
• Volume: 33
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.200323515

✦ Synopsis

Abstract

CD20 is a B cell‐specific surface antigen that is thought to play an important role in B cell activation and proliferation, possibly by functioning as a calcium channel or interacting with other cell surface molecules important in B cell signal transduction, such as CD40. In this study, it was found that stimulation through CD40 caused a dramatic decrease in the expression of surface CD20 in normal human B lymphocytes. Down‐regulation of CD20 was time and ligand concentration dependent, beginning as early as 15 min after incubation with CD40 ligand‐transfected fibroblasts. The rapid onset of this effect in the presence of stable steady‐state mRNA levels suggests that CD20 down‐regulation occurs at a nontranscriptional level. Confocal fluorescent microscopy indicates that CD20 and CD40 are internalized upon CD40 activation. Specifically, CD20 translocates into lipid rafts and is internalized into cytoplasmic vesicles, in a process that is inhibited by cytochalasin B andprotein kinase C antagonists. Paradoxically, one functional consequence of CD20 down‐regulation was enhanced calcium signaling upon CD20 cross‐linking. These observations support the notion that CD20 engages downstream signaling pathways that alter calcium homeostasis rather than functioning as a calcium channel itself, such signal transduction is enhanced upon CD20 internalization, and CD40 is a regulator of CD20‐mediated signaling.