Tumor-Derived Autophagosomes (DRibbles) Induce B Cell Activation in a TLR2-MyD88 Dependent Manner

Polymerization of the actin cytoskeleton has been found to be essential for B-cell activation. We show here, however, that stimulation of BCR induces a rapid global actin depolymerization in a BCR signal strength-dependent manner, followed by polarized actin repolymerization. Depolymerization of actin enhances and blocking actin depolymerization inhibits BCR signaling, leading to altered BCR and lipid raft clustering, ERK activation, and transcription factor activation. Furthermore actin depolymerization by itself induces altered lipid raft clustering and ERK activation, suggesting that F-actin may play a role in separating lipid rafts and in setting the threshold for cellular activation.

Download Full-text

Lipid raft–dependent plasma membrane repair interferes with the activation of B lymphocytes

The Journal of Cell Biology ◽

10.1083/jcb.201505030 ◽

2015 ◽

Vol 211 (6) ◽

pp. 1193-1205 ◽

Cited By ~ 14

Author(s):

Heather Miller ◽

Thiago Castro-Gomes ◽

Matthias Corrotte ◽

Christina Tam ◽

Timothy K. Maugel ◽

...

Keyword(s):

Plasma Membrane ◽

B Cell ◽

B Lymphocytes ◽

Lipid Rafts ◽

Lipid Raft ◽

Cell Activation ◽

Dependent Manner ◽

B Cell Activation ◽

Membrane Repair ◽

Membrane Injury

Cells rapidly repair plasma membrane (PM) damage by a process requiring Ca2+-dependent lysosome exocytosis. Acid sphingomyelinase (ASM) released from lysosomes induces endocytosis of injured membrane through caveolae, membrane invaginations from lipid rafts. How B lymphocytes, lacking any known form of caveolin, repair membrane injury is unknown. Here we show that B lymphocytes repair PM wounds in a Ca2+-dependent manner. Wounding induces lysosome exocytosis and endocytosis of dextran and the raft-binding cholera toxin subunit B (CTB). Resealing is reduced by ASM inhibitors and ASM deficiency and enhanced or restored by extracellular exposure to sphingomyelinase. B cell activation via B cell receptors (BCRs), a process requiring lipid rafts, interferes with PM repair. Conversely, wounding inhibits BCR signaling and internalization by disrupting BCR–lipid raft coclustering and by inducing the endocytosis of raft-bound CTB separately from BCR into tubular invaginations. Thus, PM repair and B cell activation interfere with one another because of competition for lipid rafts, revealing how frequent membrane injury and repair can impair B lymphocyte–mediated immune responses.

Download Full-text

Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase

eLife ◽

10.7554/elife.23060 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 20

Author(s):

Samina Shaheen ◽

Zhengpeng Wan ◽

Zongyu Li ◽

Alicia Chau ◽

Xinxin Li ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Cell Activation ◽

Underlying Mechanism ◽

Signaling Molecules ◽

Substrate Stiffness ◽

Dependent Manner ◽

B Cell Activation ◽

Cell Discrimination ◽

Cell Mechanosensing

The mechanosensing ability of lymphocytes regulates their activation in response to antigen stimulation, but the underlying mechanism remains unexplored. Here, we report that B cell mechanosensing-governed activation requires BCR signaling molecules. PMA-induced activation of PKCβ can bypass the Btk and PLC-γ2 signaling molecules that are usually required for B cells to discriminate substrate stiffness. Instead, PKCβ-dependent activation of FAK is required, leading to FAK-mediated potentiation of B cell spreading and adhesion responses. FAK inactivation or deficiency impaired B cell discrimination of substrate stiffness. Conversely, adhesion molecules greatly enhanced this capability of B cells. Lastly, B cells derived from rheumatoid arthritis (RA) patients exhibited an altered BCR response to substrate stiffness in comparison with healthy controls. These results provide a molecular explanation of how initiation of B cell activation discriminates substrate stiffness through a PKCβ-mediated FAK activation dependent manner.

Download Full-text