Down-regulation of CD20 on B cells upon CD40 activation.
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 and protein 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.
Anolik
Jennifer
J
Department of Medicine, University of Rochester School of Medicine, Rochester 14642, USA. jennifer_anolik@urmc.rochester.edu
Looney
R John
RJ
Bottaro
Andrea
A
Sanz
Iñaki
I
Young
Fay
F
D018951:Antigens, CD20 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D015536:Down-Regulation; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology* / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology
D018951:Antigens, CD20; D019013:CD40 Antigens; D011493:Protein Kinase C