Floating the raft hypothesis for immune receptors: access to rafts controls receptor signaling and trafficking.
The B cell antigen receptor (BCR) is a member of an important family of multichain immune recognition receptors, which are complexes composed of ligand-binding domains associated with signal-transduction complexes. The signaling components of these receptors have no inherent kinase activity but become tyrosine phosphorylated in their cytoplasmic domains by Src-family kinases upon oligomerization, thus initiating signaling cascades. The BCR is unique in this family in that, in addition to its signaling function, it also serves to deliver antigen to intracellular compartments where the antigen is processed and presented bound to major histocompatibility complex (MHC) class II molecules. Recent evidence indicates that both the signaling and antigen-trafficking functions of the BCR are regulated by cholesterol- and sphingolipid-rich plasma membrane microdomains termed rafts. Indeed, upon oligomerization, the BCR translocates into rafts that concentrate the Src-family kinase Lyn and is subsequently internalized directly from the rafts. Thus, translocation into rafts allows the association of the oligomerized BCR with Lyn and the initiation of both signaling and trafficking. Significantly, the access of the BCR to rafts appears to be controlled by a variety of B lymphocyte co-receptors, as well as factors including the developmental state of the B cell and viral infection. Thus, the translocation of the immune receptors into signaling-competent microdomains may represent a novel mechanism to initiate and regulate immune-cell activation.
National Institutes of Health, National Institute of Allergy and Infectious Diseases, Laboratory of Immunogenetics, Rockville, MD 20852, USA.
M L
ML
Dykstra
A
A
Cherukuri
S K
SK
Pierce
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D018448:Models, Immunological; D021381:Protein Transport; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell