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Vol. 14, Issue 2, 432-444, February 2003
Department of Microbiology and Immunology, G. W. Hooper Foundation, University of California, San Francisco, San
Francisco, California 94143
Recent biochemical evidence indicates that an early event in signal
transduction by the B-cell antigen receptor (BCR) is its translocation
to specialized membrane subdomains known as lipid rafts. We have taken
a microscopic approach to image lipid rafts and early events associated
with BCR signal transduction. Lipid rafts were visualized on primary
splenic B lymphocytes from wild-type or anti-hen egg lysozyme
BCR transgenic mice, and on a mature mouse B-cell line Bal 17 by using
fluorescent conjugates of cholera toxin B subunit or a Lyn-based
chimeric protein, which targets green fluorescent protein to the lipid
raft compartment. Time-lapse imaging of B cells stimulated via the BCR
with the antigen hen egg lysozyme, or surrogate for antigen anti-IgM,
demonstrated that lipid rafts are highly dynamic entities, which move
laterally on the surface of these cells and coalesce into large
regions. These regions of aggregated lipid rafts colocalized with the
BCR and tyrosine-phosphorylated proteins. Microscopic imaging of live B
cells also revealed an inducible colocalization of lipid rafts with the
tyrosine kinase Syk and the receptor tyrosine phosphatase CD45. These
two proteins play indispensable roles in BCR-mediated signaling but are
not detectable in biochemically purified lipid raft fractions.
Strikingly, BCR stimulation also induced the formation of long,
thread-like filopodial projections, similar to previously described
structures called cytonemes. These B-cell cytonemes are rich in lipid
rafts and actin filaments, suggesting that they might play a role in
long-range communication and/or transportation of signaling molecules
during an immune response. These results provide a window into the
morphological and molecular organization of the B-cell membrane during
the early phase of BCR signaling.
Online
version of this article contains video material for some figures.
Online version available at www.molbiolcell.org.
*
Corresponding author. E-mail address: defranco{at}cgl.ucsf.edu.
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