Translocation of the B cell antigen receptor into lipid rafts reveals a novel step in signaling.
The cross-linking of the B cell Ag receptor (BCR) leads to the initiation of a signal transduction cascade in which the earliest events involve the phosphorylation of the immunoreceptor tyrosine-based activation motifs of Ig alpha and Ig beta by the Src family kinase Lyn and association of the BCR with the actin cytoskeleton. However, the mechanism by which BCR cross-linking initiates the cascade remains obscure. In this study, using various A20-transfected cell lines, biochemical and genetic evidence is provided that BCR cross-linking leads to the translocation of the BCR into cholesterol- and sphingolipid-rich lipid rafts in a process that is independent of the initiation of BCR signaling and does not require the actin cytoskeleton. Translocation of the BCR into lipid rafts did not require the Ig alpha/Ig beta signaling complex, was not dependent on engagement of the FcR, and was not blocked by the Src family kinase inhibitor PP2 or the actin-depolymerizing agents cytochalasin D or latrunculin. Thus, cross-linking or oligomerization of the BCR induces the BCR translocation into lipid rafts, defining an event in B cell activation that precedes receptor phosphorylation and association with the actin cytoskeleton.
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
P C
PC
Cheng
B K
BK
Brown
W
W
Song
S K
SK
Pierce
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D001693:Biological Transport, Active / Q000235:genetics / Q000276:immunology; D051925:CD79 Antigens; D002462:Cell Membrane / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D003599:Cytoskeleton / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D021962:Membrane Microdomains / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013696:Temperature; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D000199:Actins; D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; C497883:CD79B protein, human; C497882:Cd79a protein, mouse; C497884:Cd79b protein, mouse; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell; D017452:Receptors, IgG; D014443:Tyrosine; D019061:src-Family Kinases