Structurally distinct endocytic pathways for B cell receptors in B lymphocytes

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• B lymphocytes are crucial for adaptive immunity, utilizing B cell receptors (BCR) to capture antigens.
• BCR clustering and internalization via endocytosis are key steps following antigen binding.
• The influence of antigen concentration on BCR endocytosis mechanisms remains poorly understood.

Purpose of the Study:

• To investigate how soluble antigen concentration affects B cell receptor (BCR) clustering and internalization.
• To elucidate the underlying mechanisms of BCR endocytosis in response to varying antigen levels.

Main Methods:

• Utilized correlative superresolution fluorescence and platinum replica electron microscopy in a human B cell line.
• Visualized nanoscale BCR clusters and their internalization pathways.
• Investigated the role of actin cytoskeleton and FCHSD2 in the endocytic process.

Main Results:

• BCR cluster size directly correlates with F(ab')2 (antigen fragment) concentration.
• A switch in endocytosis mechanism occurs: classical clathrin-mediated endocytosis for small clusters (low antigen) and large, clathrin-capped invaginations for large clusters (high antigen).
• Actin recruitment, involving FCHSD2, is essential for the formation and cytosolic capture of these large endocytic carriers.

Conclusions:

• B cells dynamically switch endocytosis mechanisms to accommodate varying sizes of BCR clusters induced by antigen concentration.
• A novel, actin-dependent endocytic pathway is employed for large BCR clusters formed at high antigen concentrations.
• Cortical actin cytoskeleton organization and dynamics are critical regulators of this antigen-concentration-dependent endocytosis.