Convergent evolution and B-cell recirculation in germinal centers in a human lymph node.

Area of Science:

• Immunology
• Molecular Biology
• Evolutionary Biology

Background:

• Germinal centers (GCs) are crucial for adaptive immunity, antibody production, and immune memory.
• Dysregulation of GCs is implicated in autoimmune diseases and cancers.
• Previous studies primarily used mouse models with specific antigens, limiting real-world applicability.

Purpose of the Study:

• To investigate the evolutionary dynamics of individual GCs within human lymph nodes during ongoing immune responses.
• To characterize B-cell clonal heterogeneity and interactions across multiple, simultaneously active GCs in humans.
• To explore potential convergent evolution of GCs in response to unknown antigens.

Main Methods:

• Laser capture microdissection of individual GCs from human lymph nodes.
• Next-generation repertoire sequencing of B-cell receptors within GCs.
• Phylogenetic tree analysis and paratope modeling.

Main Results:

• Observed significant clonal diversity within individual human GCs, similar to mouse models.
• Identified shared B-cell clones distributed across multiple distinct GCs within the same lymph node.
• Phylogenetic and modeling analyses suggested re-engagement and rediversification of clones across GCs, indicating convergent evolution.

Conclusions:

• Human GCs function as distinct evolutionary spaces with heterogeneous clonal compositions.
• Evidence supports the re-emergence and diversification of B-cell clones across multiple GCs.
• Convergent evolution of GCs, driven by shared antigen responses, is a key feature of human immune responses.