The Coordination Between B Cell Receptor Signaling and the Actin Cytoskeleton During B Cell Activation

Li, Jingwen; Yin, Wei; Jing, Yukai; Kang, Danqing; Lü, Yang; Cheng, Jiali; Yu, Ze; Peng, Zican; Li, Xingbo; Wen, Yue; Sun, Xizi; Ren, Boxu; Liu, Chaohong

doi:10.3389/fimmu.2018.03096

Cited by 56 publications

(52 citation statements)

References 135 publications

(241 reference statements)

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“…It is out of the scope of this review a detailed description of the TCR and BCR-derived signaling involved in actin cytoskeleton remodeling upon IS formation. Thus please refer to the excellent reviews on this subject [37] [33,35,[38][39][40]. In brief, TCR and BCR stimulation, together with the interaction of adhesion and costimulatory molecules at the IS, triggers the generation of several early second messengers such as calcium and diacyglycerol (DAG) [41].…”

Section: Immune Synapse and Secretory Trafficmentioning

confidence: 99%

“…The concentric F-actin architecture of the IS and the actin cytoskeleton reorganization are strikingly shared by CD4 + Th lymphocytes, CD8 + CTL, B lymphocytes, and natural killer cells (NK) [35,39]. Interestingly, all these immune cells exhibit the ability to form synapses and to directionally secrete stimulatory or cytotoxic factors at the IS.…”

Section: Immune Synapse and Secretory Trafficmentioning

confidence: 99%

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Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Calvo

Izquierdo

2020

IJMS

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Exosomes are extracellular vesicles (EV) of endosomal origin (multivesicular bodies, MVB) constitutively released by many different eukaryotic cells by fusion of MVB to the plasma membrane. However, inducible exosome secretion controlled by cell surface receptors is restricted to very few cell types and a limited number of cell surface receptors. Among these, exosome secretion is induced in T lymphocytes and B lymphocytes when stimulated at the immune synapse (IS) via T-cell receptors (TCR) and B-cell receptors (BCR), respectively. IS formation by T and B lymphocytes constitutes a crucial event involved in antigen-specific, cellular, and humoral immune responses. Upon IS formation by T and B lymphocytes with antigen-presenting cells (APC), the convergence of MVB towards the microtubule organization center (MTOC), and MTOC polarization to the IS, are involved in polarized exosome secretion at the synaptic cleft. This specialized mechanism provides the immune system with a finely-tuned strategy to increase the specificity and efficiency of crucial secretory effector functions of B and T lymphocytes. As inducible exosome secretion by antigen-receptors is a critical and unique feature of the immune system this review considers the study of the traffic events leading to polarized exosome secretion at the IS and some of their biological consequences.

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Section: Immune Synapse and Secretory Trafficmentioning

confidence: 99%

Section: Immune Synapse and Secretory Trafficmentioning

confidence: 99%

Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Calvo

Izquierdo

2020

IJMS

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“…We speculated that protein 4.1R could play an important role in regulating the fate of activated B cells based on recent reports about the regulation effects of membrane cytoskeleton in B-cell function. [33][34][35][36][37][38] In this study, we explored how cytoskeleton protein 4.1R regulates the choice for the B-cell fate of PCD or CSR in vitro.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

Cytoskeleton protein 4.1R regulates B‐cell fate by modulating the canonical NF‐κB pathway

Liang

Guo

et al. 2020

Immunology

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During the immune response, B cells can enter the memory pathway, which is characterized by class switch recombination (CSR), or they may undergo plasma cell differentiation (PCD) to secrete immunoglobulin. Both of these processes occur in activated B cells, which are reported to relate to membrane-association proteins and adaptors. Protein 4.1R acts as an adaptor, linking membrane proteins to the cytoskeleton, and is involved in many cell events such as cell activation and differentiation, and cytokine secretion. However, the effect of 4.1R on regulating B-cell fate is unclear. Here, we show an important association between B-cell fate and 4.1R. In vitro, primary B cells were stimulated with lipopolysaccharide combined with interleukin-4; results showed that 4.1R-deficient (4.1R-/-) cells compared with wild-type (4.1R +/+) B cells augmented expression of activation-induced cytidine deaminase and germline, resulting in increased IgG1 + B cells, whereas the secretion of IgG1 and IgM was reduced, and CD138 + B cells were also decreased. Throughout the process, 4.1R regulated canonical nuclear factor (NF-jB) rather than non-canonical NF-jB to promote the expression of CSR complex components, leading to up-regulation of B-cell CSR. In contrast, 4.1R-deficient B cells showed reduced expression of Blimp-1, which caused B cells to down-regulate PCD. Furthermore, over-activation of canonical NF-jB may induce apoptosis signaling to cause PCD apoptosis to reduce PCD number. In summary, our results suggest that 4.1R acts as a B-cell fate regulator by inhibiting the canonical NF-jB signaling pathway.

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“…In support of this, C-mem1 expresses networks dominantly related to antigen binding and housekeeping protein translation functions, but little else. In comparison, the three top networks of C-mem2 are actin and cytoskeleton related genes, suggestive of greater activity and regulation of the BCR leading cell to cell signalling (58).…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomic analyses define distinct peripheral B cell subsets and discrete development pathways

Stewart

Wallis

et al. 2020

Preprint

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Separation of B cells into different subsets has been useful to understand their different functions in various immune scenarios. In some instances, the subsets defined by phenotypic FACS separation are relatively homogeneous and so establishing the functions associated with them is straightforward. Other subsets, such as the “Double negative” (DN, CD19+CD27-IgD-) population, are more complex with reports of differing functionality which could indicate a heterogeneous population. Recent advances in single-cell techniques enable an alternative route to characterise cells based on their transcriptome. To maximise immunological insight, we need to match prior data from phenotype-based studies with the finer granularity of the single-cell transcriptomic signatures. We also need to be able to define meaningful B cell subsets from single cell analyses performed on PBMCs, where the relative paucity of a B cell signature means that defining B cell subsets within the whole is challenging. Here we provide a reference single-cell dataset based on phenotypically sorted B cells and an unbiased procedure to better classify functional B cell subsets in the peripheral blood, particularly useful in establishing a baseline cellular landscape and in extracting significant changes with respect to this baseline from single-cell datasets. We find 10 different clusters of B cells and applied a novel, geometry-inspired, method to RNA velocity estimates in order to evaluate the dynamical transitions between B cell clusters. This indicated the presence of two main developmental branches of memory B cells. One involves IgM memory cells and two DN subpopulations, culminating in a population thought to be associated with Age related B cells and the extrafollicular response. The other branch involves a third DN cluster which appears to be a precursor of classical memory cells. In addition, we identify a novel DN4 population, which is IgE rich and on its own developmental branch but with links to the classical memory branch.

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The Coordination Between B Cell Receptor Signaling and the Actin Cytoskeleton During B Cell Activation

Cited by 56 publications

References 135 publications

Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Inducible Polarized Secretion of Exosomes in T and B Lymphocytes

Cytoskeleton protein 4.1R regulates B‐cell fate by modulating the canonical NF‐κB pathway

Single-cell transcriptomic analyses define distinct peripheral B cell subsets and discrete development pathways

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