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Lipid rafts and B-cell activation

Nature Reviews Immunology volume 2, pages 96–105 (2002)Cite this article

Key Points

  • Lipid rafts act as platforms in B cells for B-cell receptor (BCR) signalling and antigen targeting.

  • Rafts concentrate the Src-family kinase Lyn and exclude the BCR and receptors that negatively regulate BCR signalling.

  • BCR oligomerization results in association of the BCR with lipid rafts and its phosphorylation by Lyn, initiating signalling.

  • The association of the BCR with lipid rafts changes during B-cell development, which might contribute to the differences in the outcome of antigen encounter.

  • B-cell co-receptors, including CD19–CD21 and FcγRII influence the association of the BCR with rafts, which might represent a new mechanism for co-receptor function.

  • Epstein–Barr-virus-encoded gene products LMP1 and LMP2A are constitutively associated with rafts and act within rafts to block BCR signalling, providing signals for longevity and inducing latency.

Abstract

The B-cell antigen receptor acts during B-cell activation both to initiate signalling cascades and to transport antigen into the cell for subsequent processing and presentation. Recent evidence indicates that membrane microdomains, termed lipid rafts, have a role in B-cell activation as platforms for B-cell receptor (BCR) signalling and might also act in antigen trafficking. Lipid rafts might facilitate the regulation of the BCR during B-cell development by B-cell co-receptors, and during viral infection. So, lipid rafts seem to be an important new piece of the B-cell signalling puzzle.

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Figure 1: The function of the BCR in B-cell activation.
Figure 2: Model of the role for lipid rafts in B-cell activation.
Figure 3: The B-cell receptor (BCR) and rafts in B-cell development.
Figure 4: Rafts and immune synapses.

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Author information

Authors and Affiliations

  1. National Institutes of Health, National Institute of Allergy and Infectious Diseases, Laboratory of Immunogenetics, Twinbrook II, 12441 Parklawn Drive, Room 200B, MSC 8180, Rockville, 20852, Maryland, USA

    Susan K. Pierce

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DATABASES

LocusLink

Btk

c-Abl

CD154

CD19

CD21

CD22

CD40

CD45

Lyn

PAG

phospholipase Cγ2

SHIP

SHP1

Syk

TRAF3

Vav

FURTHER INFORMATION

B lymphocytes: receptors

antibody responses: development

Glossary

ITAM

Immunoreceptor tyrosine-based activation motif, which is present in the cytoplasmic domains of the BCR Igα–Igβ complex and becomes tyrosine phosphorylated by Lyn after BCR activation.

FLUORESCENCE RESONANCE ENERGY TRANSFER

A method to determine whether proteins are close to one another by measuring the loss of fluorescence anisotropy between fluorophores that are associated with the proteins.

SINGLE FLUOROPHORE TRACKING MICROSCOPY

A method to measure the lateral motion of a single fluorescently labelled molecule in the plasma membrane using single dye tracking. It yields information about the diffusion and dynamics of individual raft proteins and lipids.

PHOTONIC FORCE MICROSCOPY

A method to measure the local viscous drag of a single membrane protein using a laser trap. It yields information about the size and dynamics of individual rafts.

ANERGY

A state of non-reactivity in B cells that is induced by antigen exposure, commonly in immature B cells

ITIM

Immunoreceptor tyrosine-based inhibitory motif that is present in the cytoplasmic domain of several inhibitory receptors that become tyrosine phosphorylated and recruits the phosphatases SHP1 and SHIP.

GERMINAL CENTRE

A specialized microenvironment in lymph nodes and spleens that forms after antigenic stimulation and is a site of extensive B-cell proliferation and somatic hypermutation of the immunoglobulin genes.

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Pierce, S. Lipid rafts and B-cell activation. Nat Rev Immunol 2, 96–105 (2002). https://doi.org/10.1038/nri726

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