CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand.
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.
Depoil
David
D
Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Fleire
Sebastian
S
Treanor
Bebhinn L
BL
Weber
Michele
M
Harwood
Naomi E
NE
Marchbank
Kevin L
KL
Tybulewicz
Victor L J
VL
Batista
Facundo D
FD
D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008051:Lipid Bilayers; D008213:Lymphocyte Activation; D051379:Mice; D008856:Microscopy, Fluorescence; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D017464:Receptors, Complement 3d / Q000502:physiology; D015398:Signal Transduction; D000072377:Syk Kinase
D018941:Antigens, CD19; D047908:Intracellular Signaling Peptides and Proteins; D008051:Lipid Bilayers; D011947:Receptors, Antigen, B-Cell; D017464:Receptors, Complement 3d; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse