Differential organization of tonic and chronic B cell antigen receptors in the plasma membrane

Castro, Maria Angela Gomes de; Wildhagen, Hanna; Sograte‐Idrissi, Shama; Hitzing, Christoffer; Binder, Mascha; Trepel, Martin; Engels, Niklas; Opazo, Felipe

doi:10.1038/s41467-019-08677-1

Cited by 51 publications

(40 citation statements)

References 66 publications

(79 reference statements)

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“…Consistent with these observations are imaging data showing that HD BCRs exist predominantly as monomers and dimers in the plasma membranes of resting B cells and form oligomeric clusters upon stimulation with antigen. In contrast, CLL BCRs form dimers and oligomers in the absence of a stimulus, reflecting an antigen-independent tonic activity of the BCR ( 72 ). A single amino acid exchange reverted the organization to monomers and thus prevented auto-aggregation of CLL BCRs ( 72 ).…”

Section: In Vivo Cll Proliferationmentioning

confidence: 99%

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Proliferative Signals in Chronic Lymphocytic Leukemia; What Are We Missing?

2020

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Chronic lymphocytic leukemia (CLL) cells cycle between lymphoid tissue sites where they actively proliferate, and the peripheral blood (PB) where they become quiescent. Strong evidence exists for a crucial role of B cell receptor (BCR) triggering, either by (self-)antigen or by receptor auto-engagement in the lymph node (LN) to drive CLL proliferation and provide adhesion. The clinical success of Bruton’s tyrosine kinase (BTK) inhibitors is widely accepted to be based on blockade of the BCR signal. Additional signals in the LN that support CLL survival derive from surrounding cells, such as CD40L-presenting T helper cells, myeloid and stromal cells. It is not quite clear if and to what extent these non-BCR signals contribute to proliferation in situ. In vitro BCR triggering, in contrast, leads to low-level activation and does not result in cell division. Various combinations of non-BCR signals delivered via co-stimulatory receptors, Toll-like receptors (TLRs), and/or soluble cytokines are applied, leading to comparatively modest and short-lived CLL proliferation in vitro . Thus, an unresolved gap exists between the condition in the patient as we now understand it and applicable knowledge that can be harnessed in the laboratory for future therapeutic applications. Even in this era of targeted drugs, CLL remains largely incurable with frequent relapses and emergence of resistance. Therefore, we require better insight into all aspects of CLL growth and potential rewiring of signaling pathways. We aim here to provide an overview of in vivo versus in vitro signals involved in CLL proliferation, point out areas of missing knowledge and suggest future directions for research.

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Section: In Vivo Cll Proliferationmentioning

confidence: 99%

“…In contrast, CLL BCRs form dimers and oligomers in the absence of a stimulus, reflecting an antigen-independent tonic activity of the BCR ( 72 ). A single amino acid exchange reverted the organization to monomers and thus prevented auto-aggregation of CLL BCRs ( 72 ).…”

Section: In Vivo Cll Proliferationmentioning

confidence: 99%

Proliferative Signals in Chronic Lymphocytic Leukemia; What Are We Missing?

2020

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“…This cellular model allows simple visual inspection and numerical analysis because the POIs are evenly distributed in the cellular surface of these resting B cells. 29 Cells were first stained and then chemically fixed with aldehydes to be imaged under stimulation emission depletion (STED) microscopy. Initially, the surface IgM-BCRs on living Ramos cells were stained using fluorescent-monovalent probes: a monoclonal affibody 29 or a polyclonal single Fab fragment (polyFab) (Fig.…”

Section: Secondary Nanobodies Reduce the Probe-induced Clusters Of Tamentioning

confidence: 99%

Circumvention of common labelling artefacts using secondary nanobodies

et al. 2020

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“…It is also unclear whether tetraspanin distribution differs between normal and malignant cells. Such effects have been described, e.g., for organisation of B-cell receptor complex [ 23 ].…”

Section: Introduction To the Tetraspanin Family Of Proteinsmentioning

confidence: 99%

Tetraspanins in the regulation of mast cell function

Orinska

Hagemann

Hálová

et al. 2020

Med Microbiol Immunol

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Mast cells (MCs) are long-living immune cells highly specialized in the storage and release of different biologically active compounds and are involved in the regulation of innate and adaptive immunity. MC degranulation and replacement of MC granules are accompanied by active membrane remodelling. Tetraspanins represent an evolutionary conserved family of transmembrane proteins. By interacting with lipids and other membrane and intracellular proteins, they are involved in organisation of membrane protein complexes and act as “molecular facilitators” connecting extracellular and cytoplasmic signaling elements. MCs express different tetraspanins and MC degranulation is accompanied by changes in membrane organisation. Therefore, tetraspanins are very likely involved in the regulation of MC exocytosis and membrane reorganisation after degranulation. Antiviral response and production of exosomes are further aspects of MC function characterized by dynamic changes of membrane organization. In this review, we pay a particular attention to tetraspanin gene expression in different human and murine MC populations, discuss tetraspanin involvement in regulation of key MC signaling complexes, and analyze the potential contribution of tetraspanins to MC antiviral response and exosome production. In-depth knowledge of tetraspanin-mediated molecular mechanisms involved in different aspects of the regulation of MC response will be beneficial for patients with allergies, characterized by overwhelming MC reactions.

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Differential organization of tonic and chronic B cell antigen receptors in the plasma membrane

Cited by 51 publications

References 66 publications

Proliferative Signals in Chronic Lymphocytic Leukemia; What Are We Missing?

Proliferative Signals in Chronic Lymphocytic Leukemia; What Are We Missing?

Circumvention of common labelling artefacts using secondary nanobodies

Tetraspanins in the regulation of mast cell function

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