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Published on: April 9, 2018
CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to
David Depoil1, Sebastian Fleire, Bebhinn L Treanor
1Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Insights
The B cell antigen receptor (BCR) signalosome
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- B cell activation is crucial for adaptive immunity.
- Early signaling events dictate B cell responses.
Purpose of the Study:
- To elucidate the spatiotemporal organization of the BCR signalosome during early B cell activation.
- To define the role of CD19 in BCR-dependent signaling.
Main Methods:
- High-resolution imaging of mouse B cells.
- Analysis of receptor and signaling molecule dynamics.
- Genetic deficiency models (CD19-deficient B cells).
Main Results:
- BCR microclusters form upon ligand stimulation, recruiting Syk and associating with CD19.
- CD19-deficient B cells show impaired signaling initiation, effector accumulation, and cell spreading.
- Microcluster formation was reduced in CD19-deficient B cells.
Conclusions:
- CD19 plays an essential, costimulatory molecule CD21-independent role in amplifying early B cell activation.
- The study defines the dynamics of BCR signalosome assembly and highlights CD19's critical function.
Abstract:
Here we describe the spatiotemporal architecture, at high molecular resolution, of receptors and signaling molecules during the early events of mouse B cell activation. In response to membrane-bound ligand stimulation, antigen aggregation occurs in B cell antigen receptor (BCR) microclusters containing immunoglobulin (Ig) M and IgD that recruit the kinase Syk and transiently associate with the coreceptor CD19. Unexpectedly, CD19-deficient B cells were significantly defective in initiation of BCR-dependent signaling, accumulation of downstream effectors and cell spreading, defects that culminated in reduced microcluster formation. Hence, we have defined the dynamics of assembly of the main constituents of the BCR 'signalosome' and revealed an essential role for CD19, independent of the costimulatory molecule CD21, in amplifying early B cell activation events in response to membrane-bound ligand stimulation.
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