Antigen presentation to B cells

B cells are capable of mounting responses to a bewildering range of potentially pathogenic antigens through the production of high-affinity antibodies and the establishment of immunological memory. Thus, regulated B-cell activation is critical for protection against a variety of bacterial and viral infections, as well as cancers. Here, we discuss a number of recent imaging studies that have provided new insights into the variety of mechanisms by which B-cell activation is initiated in the lymph node in vivo

A talin-dependent LFA-1 focal zone is formed by rapidly migrating T lymphocytes

Cells such as fibroblasts and endothelial cells migrate through the coordinated responses of discrete integrin-containing focal adhesions and complexes. In contrast, little is known about the organization of integrins on the highly motile T lymphocyte. We have investigated the distribution, activity, and cytoskeletal linkage of the integrin lymphocyte function associated antigen-1 (LFA-1) on human T lymphocytes migrating on endothelial cells and on ligand intercellular adhesion molecule-1 (ICAM-1). The pattern of total LFA-1 varies from low expression in the lamellipodia to high expression in the uropod. However, high affinity, clustered LFA-1 is restricted to a mid-cell zone that remains stable over time and over a range of ICAM-1 densities. Talin is essential for the stability and formation of the LFA-1 zone. Disruption of the talin–integrin link leads to loss of zone integrity and a substantial decrease in speed of migration on ICAM-1. This adhesive structure, which differs from the previously described integrin-containing attachments displayed by many other cell types, we have termed the “focal zone.

Daughter B cells are not created equal: Asymmetric segregation of antigen during B cell division

Comment on: Thaunat O, et al. Science 2012; 335:475-9

Phospholipase C-γ2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen

B cell receptor (BCR) recognition of membrane-bound antigen initiates a spreading and contraction response, the extent of which is controlled through the formation of signaling-active BCR-antigen microclusters and ultimately affects the outcome of B cell activation. We followed a genetic approach to define the molecular requirements of BCR-induced spreading and microcluster formation. We identify a key role for phospholipase C-γ2 (PLCγ2), Vav, B cell linker, and Bruton's tyrosine kinase in the formation of highly coordinated “microsignalosomes,” the efficient assembly of which is absolutely dependent on Lyn and Syk. Using total internal reflection fluorescence microscopy, we examine at high resolution the recruitment of PLCγ2 and Vav to microsignalosomes, establishing a novel synergistic relationship between the two. Thus, we demonstrate the importance of cooperation between components of the microsignalosome in the amplification of signaling and propagation of B cell spreading, which is critical for appropriate B cell activation

Neutrophils—the unexpected helpers of B‐cell activation

A specific subpopulation of neutrophils, termed N(BH), has been shown recently to provide help for the differentiation and function of B cells and plasma cells. These novel findings are put in the context of our current understanding of B-cell help

Dynamic cortical actin remodeling by ERM proteins controls BCR microcluster organization and integrity

By dynamically remodeling the cortical actin network, ezrin and moesin control BCR microcluster formation, organization, and integrity

The B-cell antigen receptor signals through a preformed transducer module of SLP65 and CIN85

The Slp65 adaptor molecule is important for B-cell receptor signalling. Here, the interactomes of SLP65 in resting and activated B cells are resolved by mass spectrometry. A number of SLP65 interacting partners, including CIN85, continuously associate with SLP65 in a stimulation-independent manner. CIN85 recruits SLP65 to the membrane and it is required for SLP65 phosphorylation