LFA-1/ICAM-1 Interaction Lowers the Threshold of B Cell Activation by Facilitating B Cell Adhesion and Synapse Formation

Carrasco, Yolanda R.; Fleire, Sebastian J.; Cameron, Thomas O.; Dustin, Michael L.; Batista, Facundo D.

doi:10.1016/s1074-7613(04)00105-0

Cited by 328 publications

(395 citation statements)

References 60 publications

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“…Interestingly, B cells have been shown to acquire antigen from antigen-presenting cells after formation of synapses, which are characterized by a central supramolecular activation cluster-containing antigen-bound BCR and PLC␥ 2 at high densities. The cSMACs are surrounded by peripheral rings, referred to pSMACs, containing high concentrations of integrins such as LFA-1 (73,74). The interaction of LFA-1 with its main ligand, ICAM-1, which is present on leukocytes, follicular dendritic cells, dendritic cells, and vascular endothelial cells (74), has been shown to lower the threshold of B cell activation (75).…”

Section: Discussionmentioning

confidence: 99%

Isozyme-specific Stimulation of Phospholipase C-γ2 by Rac GTPases

Piechulek

Rehlen

Walliser

et al. 2005

Journal of Biological Chemistry

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The regulation of the two isoforms of phospholipase C-␥, PLC␥ 1 and PLC␥ 2 , by cell surface receptors involves protein tyrosine phosphorylation as well as interaction with adapter proteins and phosphatidylinositol 3,4,5-trisphosphate (PtdInsP 3 ) generated by inositol phospholipid 3-kinases (PI3Ks). All three processes may lead to recruitment of the PLC␥ isozymes to the plasma membrane and/or stimulation of their catalytic activity. Recent evidence suggests that PLC␥ may also be regulated by Rho GTPases. In this study, PLC␥ 1 and PLC␥ 2 were reconstituted in intact cells and in a cell-free system with Rho GTPases to examine their influence on PLC␥ activity. PLC␥ 2 , but not PLC␥ 1 , was markedly activated in intact cells by constitutively active Rac1 G12V , Rac2 G12V , and Rac3 G12V but not by Cdc42 G12V and RhoA G14V . The mechanism of PLC␥ 2 activation was apparently independent of phosphorylation of tyrosine residues known to be modified by PLC␥ 2 -activating protein-tyrosine kinases. Activation of PLC␥ 2 by Rac2 G12V in intact cells coincided with a translocation of PLC␥ 2 from the soluble to the particulate fraction. PLC␥ isozyme-specific activation of PLC␥ 2 by Rac GTPases (Rac1 ≈ Rac2 > Rac3), but not by Cdc42 or RhoA, was also observed in a cell-free system. Herein, activation of wild-type Rac GTPases with guanosine 5-(3-O-thio)triphosphate caused a marked stimulation of PLC␥ 2 but had no effect on the activity of PLC␥ 1 . PLC␥ 1 and PLC␥ 2 have previously been shown to be indiscriminately activated by PtdInsP 3 in vitro. Thus, the results suggest a novel mechanism of PLC␥ 2 activation by Rac GTPases involving neither protein tyrosine phosphorylation nor PI3K-mediated generation of PtdInsP 3 .Inositol phospholipid-specific phospholipases C (PLCs) 3 catalyze the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP 2 ) to produce inositol 1,4,5-trisphosphate and diacylglycerol. While the products of this reaction have long been known to act as intracellular second messengers (reviewed in Refs. 1-4), it has only recently become clear that the phospholipid substrate itself may also be considered an intracellular signaling molecule in that its local concentration in the plasma membrane and possibly in other cellular membranes regulates the activities and/or subcellular distribution of a number of regulatory or structural proteins. These include enzymes, ion channels and transporters, transcription factors, scaffolding proteins, cytoskeletal proteins, as well as proteins involved in the regulation of exocytosis, endocytosis, and membrane trafficking (reviewed in Refs. 5-8).The mammalian PLCs are divided into six subfamilies, designated ␤, ␥, ␦, ⑀, , and (reviewed in Refs. 9 and 10). The four members of the PLC␤ subfamily are activated by ␤␥ dimers of heterotrimeric G proteins and/or members of the ␣ q subfamily of G protein ␣ subunits and by certain Rho GTPases (11-14). The two members of the PLC␥ family are activated by receptor and nonreceptor protein-tyrosine kinases (reviewed in Refs. 9, 10, 15, ...

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Section: Discussionmentioning

confidence: 99%

Isozyme-specific Stimulation of Phospholipase C-γ2 by Rac GTPases

Piechulek

Rehlen

Walliser

et al. 2005

Journal of Biological Chemistry

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“…Planar lipid bilayers containing anti-mouse  light chain (HB-58; American Type Culture Collection) were prepared in FCS2 chambers (Bioptechs Inc.) by liposome spreading as previously described (Carrasco et al, 2004). In brief, Alexa Fluor 633 streptavidin (Molecular Probes) was incorporated into lipid bilayers at density of 30 molecules/µm 2 , to which monobiotinylated antigen was tethered.…”

Section: Methodsmentioning

confidence: 99%

Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity

Burbage¹,

Keppler²,

Gasparrini³

et al. 2015

J Cell Biol

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The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-deficient mice are incapable of forming germinal centers or generating plasma B cells upon either viral infection or immunization. Such severe immune deficiency is caused by multiple and profound B cell abnormalities, including early blocks during B cell development; impaired antigen-driven BCR signaling and actin remodeling; defective antigen presentation and in vivo interaction with T cells; and a severe B cell-intrinsic block in plasma cell differentiation. Thus, our study presents a new perspective on Cdc42 as key regulator of B cell physiology.

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“…This translates to 64-160 molecules/µm 2 underneath the cell, which is similar to cellular densities of CD58 (150 molecules/µm 2 ). Anti-CD3 antibody was monobiotinylated following the procedure of Carrasco et al (2004). Fluorescent streptavidin and monobiotinylated anti-CD3 antibody were reacted sequentially and conjugated with biotinylated lipids in a planar bilayer , assuming two sites of biotins in lipid bilayers were occupied by one streptavidin.…”

Section: Preparation Of Planar Lipid Bilayersmentioning

confidence: 99%