Dynamic reorganisation of intermediate filaments coordinates early B-cell activation

Area of Science:

• Immunology
• Cell Biology
• Cytoskeletal Dynamics

Background:

• Cytoskeletal reorganisation is vital for B-cell activation responses.
• The role of intermediate filaments (IFs) in B cells remains poorly understood.
• Vimentin is a key component of the mammalian cytoskeleton.

Purpose of the Study:

• To investigate the dynamic reorganisation of IFs in B cells during activation.
• To determine the role of vimentin in B-cell function, including intracellular trafficking and antigen presentation.

Main Methods:

• Utilised multiple super-resolution microscopy techniques, including direct stochastic optical reconstruction microscopy (dSTORM).
• Analysed B-cell development, signalling, and differentiation in wild-type and vimentin-deficient B cells.
• Assessed intracellular trafficking of antigen-containing and lysosomal compartments (LAMP1+).
• Evaluated antigen presentation and in vivo antibody responses.

Main Results:

• IFs undergo significant reorganisation in B cells immediately after antigen stimulation.
• This IF reorganisation is dependent on actin and microtubules.
• Vimentin-deficient B cells show altered positioning of antigen and LAMP1+ compartments.
• Vimentin loss did not affect B-cell development, signalling, or differentiation.
• Vimentin-deficient B cells exhibit impaired antigen presentation and delayed antibody responses in vivo.

Conclusions:

• Intermediate filaments, specifically vimentin, play a crucial role in fine-tuning intracellular trafficking in B cells.
• Vimentin is essential for efficient antigen presentation and timely antibody responses following B-cell activation.
• This study reveals a novel function for IFs in the dynamic processes of B-cell activation.