A role for lipid rafts in B cell antigen receptor signaling and antigen targeting.
The B cell antigen receptor (BCR) serves both to initiate signal transduction cascades and to target antigen for processing and presentation by MHC class II molecules. How these two BCR functions are coordinated is not known. Recently, sphingolipid- and cholesterol-rich plasma membrane lipid microdomains, termed lipid rafts, have been identified and proposed to function as platforms for both receptor signaling and membrane trafficking. Here we show that upon cross-linking, the BCR rapidly translocates into ganglioside G(M1)-enriched lipid rafts that contain the Src family kinase Lyn and exclude the phosphatase CD45R. Both Igalpha and Lyn in the lipid rafts become phosphorylated, and subsequently the BCR and a portion of G(M1) are targeted to the class II peptide loading compartment. Entry into lipid rafts, however, is not sufficient for targeting to the antigen processing compartments, as a mutant surface Ig containing a deletion of the cytoplasmic domain is constitutively present in rafts but when cross-linked does not internalize to the antigen processing compartment. Taken together, these results provide evidence for a role for lipid rafts in the initial steps of BCR signaling and antigen targeting.
Cheng
P C
PC
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Dykstra
M L
ML
Mitchell
R N
RN
Pierce
S K
SK
D000818:Animals; D002784:Cholesterol / Q000276:immunology; D003432:Cross-Linking Reagents; D005677:G(M1) Ganglioside / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D017493:Leukocyte Common Antigens / Q000276:immunology*; D016393:Lymphoma, B-Cell; D008563:Membrane Lipids / Q000276:immunology*; D051379:Mice; D016296:Mutagenesis; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D017384:Sequence Deletion; D015398:Signal Transduction / Q000276:immunology*; D013107:Sphingolipids / Q000276:immunology; D014407:Tumor Cells, Cultured; D018909:src Homology Domains
D003432:Cross-Linking Reagents; D000949:Histocompatibility Antigens Class II; D008563:Membrane Lipids; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D013107:Sphingolipids; D005677:G(M1) Ganglioside; D002784:Cholesterol; D006735:Horseradish Peroxidase; D017493:Leukocyte Common Antigens