Visualizing the molecular and cellular events underlying the initiation of B-cell activation.
The appropriate activation of B cells is critical for the development of effective immune responses. B cell activation is initiated following the engagement of the B cell receptor (BCR) with specific antigen. The spatiotemporal characterization of the ensuing molecular and cellular events has been the subject of recent high-resolution imaging investigations. In this review we highlight information gathered thus far concerning the initial processes underlying the activation of B cells. First, we consider studies that have offered new insights into the early molecular events that occur within the B cell prior to formation of the immunological synapse. As such, BCR-microclusters formed on engagement with antigen have been identified as the sites of active signaling and assembly of "microsignalosomes." Furthermore, signaling through these "microsignalosomes" is propagated and enhanced through B cell spreading in response to membrane-antigen in a CD19-dependent manner. Finally, we discuss a number of multiphoton microscopy studies that have enabled dynamic characterization of the initial encounters between B cells and antigen in vivo. These investigations visualize the presentation of larger antigens to B cells via cell-mediated strategies, involving macrophages in the subcapsular sinus and dendritic cells in the paracortex.
Harwood
Naomi E
NE
Lymphocyte Interaction Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London, UK. facundo.batista@cancer.org.uk
Batista
Facundo D
FD
D000818:Animals; D017951:Antigen Presentation; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D036641:Microscopy, Fluorescence, Multiphoton / Q000295:instrumentation / Q000379:methods*; D015398:Signal Transduction
D018941:Antigens, CD19