B cells acquire antigen from target cells after synapse formation

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Abstract

Soluble antigen binds to the B-cell antigen receptor and is internalized for subsequent processing and the presentation of antigen-derived peptides to T cells1. Many antigens are not soluble, however, but are integral components of membrane; furthermore, soluble antigens will usually be encountered in vivo in a membrane-anchored form, tethered by Fc or complement receptors2,3,4. Here we show 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 antigens from the target. B-cell antigen receptor accumulates at the synapse, segregated from the CD45 co-receptor which is excluded from the synapse, and there is a corresponding polarization of cytoplasmic effectors in the B cell. B-cell antigen receptor mediates the gathering of antigen into the synapse and its subsequent acquisition, thereby potentiating antigen processing and presentation to T cells with high efficacy. Synapse formation and antigen acquisition will probably enhance the activation of B cells at low antigen concentration, allow context-dependent antigen recognition and enhance the linking of B- and T-cell epitopes.

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Figure 1: Synapse formation between B cell and antigen-displaying target cell.
Figure 2: Polarization of the B cell after encountering membrane-immobilized antigen.
Figure 3: Parameters affecting synapse formation.
Figure 4: Downregulation of surface BCR after antigen encounter.
Figure 5: B cells acquire and present integral membrane antigens from the target cell.

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Acknowledgements

We thank B. Amos and S. Reichelt for help and advice with confocal microscopy, and S. Munro for helpful discussions. We are indebted those who provided antibodies, transgenic mice and cell lines. F.D.B. and D.I. were supported by the Arthritis Research Campaign and Studienstiftung des deutschen Volkes, respectively.

Author information

Correspondence to Facundo D. Batista or Michael S. Neuberger.

Supplementary information

Supplement to Figure 2(d)

Polarisation of actin (stained with phalloidin), phospholipase Cg2 (PLCg2) and ganglioside GM1 (stained with cholera toxin B subunt, CTB) in HEL-specific B cells interacting with J[mHEL]6 targets. In each case, a single confocal section is shown in single or merged channel viewing.

Movie 1

Rotation of a 3D projection of HEL-specific splenic B cells that have been incubated for 10 min at 37 oC with J[mHEL]6 targets prior to fixation, permeabilisation and staining for IgM (red) and HEL (green).

Movie 2

Rotation of a 3D projection of HEL-specific splenic B cells that have been incubated for 60 min at 37 oC with J[mHEL]6 targets prior to fixation, permeabilisation and staining for IgM (red) and HEL (green). Following this longer incubation, transfer is observed of HEL to the B cell where it colocalises with IgM.

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Batista, F., Iber, D. & Neuberger, M. B cells acquire antigen from target cells after synapse formation. Nature 411, 489–494 (2001) doi:10.1038/35078099

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