Viewing the antigen‐induced initiation of B‐cell activation in living cells

  title={Viewing the antigen‐induced initiation of B‐cell activation in living cells},
  author={Pavel Tolar and Hae Won Sohn and Susan K. Pierce},
  journal={Immunological Reviews},
Summary: The binding of antigen to the B‐cell receptor (BCR) induces BCR clustering and signaling cascades that lead to the activation of a variety of genes associated with B‐cell activation. Over the last several years, our understanding of the molecular details of the BCR signaling pathways have been considerably advanced; what remains only poorly understood are the molecular events that initiate BCR clustering and how clustering leads to activation. Here, we review our progress using live… 

It's all about change: the antigen-driven initiation of B-cell receptor signaling.

With the advent of new live-cell imaging technologies, scientists are gaining their first clear views of the events that lead up to the triggering of BCR signaling cascades, which may provide potential new targets for therapeutic intervention in disease involving hyper or chronic activation of B cells.

The molecular assembly and organization of signaling active B‐cell receptor oligomers

What is known about the initiation of the antigen‐driven BCR signal transduction in the newly emerging context of B‐cell recognition of antigens presented by antigen‐presenting cells in lymphoid tissues is described.

B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk

Using a high-resolution proximity ligation assay to monitor the conformation of the BCR and its interactions with co-receptors at a 10–20 nm resolution, direct evidence is provided for the opening of BCR dimers during B cell activation and it is shown that upon binding Syk opens the receptor by an inside-out signaling mechanism that amplifies BCR signaling.

Actin‐mediated feedback loops in B‐cell receptor signaling

How actin remodels its organization and dynamics in close coordination with BCR signaling and how act in remodeling in turn amplifies the activation and subsequent downregulation process of B CR signaling, providing vital feedback for optimal BCR activation is discussed.

Monte Carlo study of B-cell receptor clustering mediated by antigen crosslinking and directed transport

It is shown that directed transport of BCRs is needed to drive the formation of large macroclusters, and a simple model of directed transport, where BCR molecules diffuse towards the largest cluster or towards a random BCR microcluster, which results in a single macrocluster of receptor molecules.

A Balance of Bruton’s Tyrosine Kinase and SHIP Activation Regulates B Cell Receptor Cluster Formation by Controlling Actin Remodeling

It is shown that both the stimulatory Bruton’s tyrosine kinase (Btk) and the inhibitory SHIP-1 are required for efficient BCR self-aggregation and a novel feedback loop between BCR signaling and the actin cytoskeleton is suggested.

The actin cytoskeleton coordinates the signal transduction and antigen processing functions of the B cell antigen receptor

How actin remodeling translates B CR signaling into rapid antigen uptake and processing while providing positive and negative feedback to BCR signaling is discussed.

The regulation of B cell activation by membrane damage and antigen density

It was discovered that BCR activation interferes with plasma membrane repair, while wounding inhibits BCR signaling and internalization by segregating BCRs from lipid rafts, and manipulations of molecular configuration and density can be applied to enhance the immunogenicity of vaccines.



The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer

Binding of antigen to the B cell antigen receptor (BCR) triggers signaling that ultimately leads to B cell activation. Using quantitative fluorescence resonance energy transfer imaging, we provide

Fluorescence resonance energy transfer in living cells reveals dynamic membrane changes in the initiation of B cell signaling.

FRET measurements in living B cells revealed highly dynamic and regulated antigen-induced changes in the plasma membrane, allowing association of the BCR with the earliest components of its signaling cascade.

Molecular Mechanisms of B Cell Antigen Receptor Trafficking

Observations indicate that the activation and recruitment of signaling molecules by the BCR orchestrate a complex series of cellular responses that favor the presentation of even rare or low‐affinity antigens if encountered in contexts indicative of infection.

B‐cell activation by membrane‐bound antigens is facilitated by the interaction of VLA‐4 with VCAM‐1

The results show that the VLA‐4/VCAM‐1 interaction during membrane antigen recognition enhances B‐cell activation and this function appears to be independent of its final peripheral localization at the IS.

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

It is shown that upon cross-linking, the BCR rapidly translocates into ganglioside GM1-enriched lipid rafts that contain the Src family kinase Lyn and exclude the phosphatase CD45R, which provides evidence for a role for lipid rafting in the initial steps of BCR signaling and antigen targeting.

Co-capping of ras proteins with surface immunoglobulins in B lymphocytes

It is demonstrated that p2lras can migrate in a directed manner along the plasma membrane and suggest that p21ras may be a component of the signalling pathway initiated by the capping of surface immunoglobulin in B lymphocytes.

Lipid rafts and B-cell activation

  • S. Pierce
  • Biology, Medicine
    Nature Reviews Immunology
  • 2002
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.

B cells acquire antigen from target cells after synapse formation

It is shown that B-cell interaction with antigens that are immobilized on the surface of a target cell leads to the formation of a synapse and the acquisition, even, of membrane-integral antigen from the target.

Location is everything: lipid rafts and immune cell signaling.

Research into the molecular basis of the spatial segregation and organization of signaling receptors provided by rafts is adding fundamentally to the understanding of the initiation and prolongation of signals in the immune system.