The role of integrins and coreceptors in refining thresholds for B‐cell responses

Abstract

Despite compelling evidence that a large proportion of antigens encountered in vivo by B cells are membrane bound, the general view is that B cells are mainly activated by soluble antigens. This notion may have been biased somewhat over the years because the high affinity of the B-cell receptor (BCR) for soluble intact ligands allows efficient B-cell stimulation in vitro. In vivo, however, even soluble antigens are likely to be deposited on the surface of antigen-presenting cells, either by complement or Fc receptors in the form of immune complexes, thus becoming more potent stimulators of B-cell activation. In this framework, the BCR works in a complex environment of integrins and coreceptors, as well as the B-cell cytoskeleton. Over the last few years, we have focused on B-cell membrane-bound antigen recognition. Here, we discuss some of our findings in the context of what is currently known in this exciting new field.

Immune Complex-Mediated Enhancement of Secondary Antibody Responses

“…However, activation by membrane-bound ICs incorporates the BCR into a synapse of integrins and coreceptors that lower the signaling threshold required for B cell activation and result in more rapid Ab responses (31). Either FcgRs or complement could anchor these ICs to the cell surface, and whereas complement can also be involved in B cell costimulation through CD21, our results suggest that it is FcgRs rather than complement that give ICs their functionality in secondary Ab responses.…”

Human peripheral blood B‐cell compartments: A crossroad in B‐cell traffic

“…Ag-specific stimulation of B-cells is typically mediated by the BCR (sIg/CD79 a/b ) coligation in the context of BCR coreceptor (CD19/CD21/CD81/CD225) and other surface molecule (CD20/CD45) costimulatory signals (76)(77)(78). The activation signal is counterbalanced by negative regulators such as CD5 and CD22, associated with signaling complexes that recruit phosphatases to protect from uncontrolled self-reactivity and even autoimmunity (78)(79)(80)(81).…”

“…The activation signal is counterbalanced by negative regulators such as CD5 and CD22, associated with signaling complexes that recruit phosphatases to protect from uncontrolled self-reactivity and even autoimmunity (78)(79)(80)(81). The balance between BCR binding, the activation of the surface costimulatory molecules, and the negative regulators drives the first step of the Ag-induced response (76)(77)(78)82).…”

The gap junction protein Cx43 regulates B-lymphocyte spreading and adhesion

“…The process of B-cell spreading is important during interactions with APCs and during the process of transendothelial migration (TEM) through vascular endothelial cells, where it is required for maximal adhesion before extravasation (Batista et al, 2007;Ley et al, 2007). Similarly to BCR-mediated spreading, LFA-1-induced spreading is also dependent on Rap1 activation (Lin et al, 2008).…”