Formation of the B cell synapse: retention or recruitment?

Abstract

Interaction of B cells with membrane antigen results in the formation of the B cell synapse: the B cell receptor (BCR) and antigen concentrate in the contact zone while CD45/B220 and the phosphatase SHP-1 are excluded. This study shows that, unlike in T cells, synapse formation does not require active transport processes (while subsequent antigen extraction and IgM downregulation do). The synapse architecture depends on the available protein ligands in the contact zone. Thus Syk, IgM and Fc receptor accumulation require the presence of ITAM-bearing BCRs, membrane antigen and membrane (IgG-containing) immune complexes, respectively. Remarkably, non-bound proteins are frequently not only homogeneously distributed but excluded from the contact zone. These results suggest that proteins mainly reach the contact zone by undirected diffusion, and in order not to be expelled by molecular crowding they require capture by and fixation to a binding protein.

Modeling of B cell Synapse Formation by Monte Carlo Simulation Shows That Directed Transport of Receptor Molecules Is a Potential Formation Mechanism

“…3a and 3e). This is to be expected in the absence of driving factors for BCR/Ag complex clustering, such as a difference in bond length or bond stiffness between BCR/Ag complexes and LFA-1/ICAM-1 complexes 4,18,25,31. A significant increase in BCR/Ag complex clustering is observed when their biasing factor η BA is set to 1.1 (Figs.…”

“…A considerable modeling effort has been expended to understand the formation mechanisms of the immunological synapse, particularly for the T cell synapse,4,9,10,16,22,23,25,26,33 and to a lesser extent the B cell synapse,15,18,31,32 although many aspects of synapse formation still remain unresolved. In T cells, differences in equilibrium bond length between TCR/MHCp and LFA-1/ICAM-1 complexes are thought to be sufficient to generate immunological synapses (the so-called “topographic model”) 25,26.…”

Capture of plasma membrane fragments from target cells by trogocytosis requires signaling in T cells but not in B cells

“…In addition, the literature provides several examples of signalingindependent events of B-cell biology including BCR endocytosis with antigen (see Caballero et al 31 and references therein), BCR recruitment into lipid rafts, 32 antigen capture by B cells, 33 and, in one study, 33 but not in another one, 26 the formation of immunologic synapses between APCs and B cells. Our data now extend this list of signaling-independent events in B-cell biology to include membrane capture by trogocytosis.…”

A very rapid and simple assay based on trogocytosis to detect and measure specific T and B cell reactivity by flow cytometry

“…To determine if reactive B cells could also be detected with our method, we made use of the system previously used by Batista et al to demonstrate the acquisition of membrane-bound antigen by B cells [18][19][20]. It consists of the B cells from the MD4 transgenic mice, which express a BCR specific for hen egg lysozyme (HEL).…”