Dynamics of local B cell migration during affinity maturation in the human tonsil

Area of Science:

• Immunology
• Cell Biology
• Systems Biology

Background:

• Germinal centers are key sites for B cell affinity maturation.
• Spatial structure in germinal centers restricts B cell movement, preserving sequence diversity.
• B cell lineage spreading across multiple germinal centers is observed but poorly understood.

Purpose of the Study:

• To investigate the sources, rates, and consequences of B cell migration between germinal centers.
• To understand the role of local migration in the spatial arrangement of B cells during affinity maturation.
• To determine the evolutionary dynamics of migrating B cell lineages.

Main Methods:

• Evolutionary re-analysis of spatial transcriptomics data from human tonsils.
• Quantitative analysis of B cell migration rates relative to cell division.
• Tracking of B cell lineage evolution and diversification in new germinal centers.

Main Results:

• B cell spatial arrangement in human tonsils is driven by local migration during affinity maturation.
• B cell migration follows a clock-like process at an average rate of approximately 1/50 cell divisions.
• Migrating B cells continue to evolve and diversify at similar rates in new germinal centers, contributing to lineage size.

Conclusions:

• Affinity maturation involves pervasive but intermediate B cell migration.
• Local migration balances diversity and selection within germinal centers.
• Understanding B cell migration dynamics is crucial for immune response mechanisms.