A Role for Lipid Rafts in B Cell Antigen Receptor Signaling and Antigen Targeting

doi:10.1084/jem.190.11.1549

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© The Rockefeller University Press, 0022-1007/1999/12/1549/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 11, December 6, 1999 1549-1560

Original Article

A Role for Lipid Rafts in B Cell Antigen Receptor Signaling and Antigen Targeting

Paul C. Cheng^a, Michelle L. Dykstra^a, Richard N. Mitchell^b, and Susan K. Pierce^a
^a Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208
^b Immunology Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115

The B cell antigen receptor (BCR) serves both to initiate signaltransduction cascades and to target antigen for processing andpresentation by MHC class II molecules. How these two BCR functionsare coordinated is not known. Recently, sphingolipid- and cholesterol-richplasma membrane lipid microdomains, termed lipid rafts, havebeen identified and proposed to function as platforms for bothreceptor signaling and membrane trafficking. Here we show thatupon cross-linking, the BCR rapidly translocates into gangliosideG_M1-enriched lipid rafts that contain the Src family kinaseLyn and exclude the phosphatase CD45R. Both Ig ${alpha}$ and Lyn in thelipid rafts become phosphorylated, and subsequently the BCRand a portion of G_M1 are targeted to the class II peptide loadingcompartment. Entry into lipid rafts, however, is not sufficientfor targeting to the antigen processing compartments, as a mutantsurface Ig containing a deletion of the cytoplasmic domain isconstitutively present in rafts but when cross-linked does notinternalize to the antigen processing compartment. Taken together,these results provide evidence for a role for lipid rafts inthe initial steps of BCR signaling and antigen targeting.

Key Words: membrane microdomain, B lymphocyte, immunoglobulin, Ig ${alpha}$ /Igß,endocytosis

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