Cutting Edge: Ig H Chains Are Sufficient to Determine Most B Cell Clonal Relationships

Area of Science:

• Immunology
• Computational Biology
• Genomics

Background:

• B cell clonal expansion is crucial for adaptive immunity.
• High-throughput sequencing of B cell receptors (BCRs) aids in studying this expansion.
• Current computational methods often rely solely on the BCR heavy (H) chain for clonal inference due to challenges in preserving B cell receptor H:L chain pairing.

Purpose of the Study:

• To assess the utility of paired B cell receptor (BCR) light (L) chains in refining clonal relationship inference.
• To evaluate the accuracy of heavy (H) chain-based clonal clustering in identifying B cell clones.
• To determine if L chains can improve H chain-based clonal clusters.

Main Methods:

• Utilized human single-cell paired BCR sequencing datasets.
• Performed computational inference to identify clonal relationships based on BCR H chain sequences.
• Assessed the impact of L chain consistency on the accuracy of H chain-based clonal clusters.
• Analyzed junction sequences and V segment mutations in misclustered clones.

Main Results:

• B cell receptor (BCR) heavy (H) chain-based clustering successfully identified clonal relationships with high confidence.
• Less than 20% of expanded clones identified by H chain analysis contained inconsistent L chains.
• Misclustered clones exhibited more divergent junction sequences and fewer shared V segment mutations in their H chains compared to accurately clustered clones.
• Paired L chains did not significantly refine the H chain-based clonal clusters.

Conclusions:

• The B cell receptor (BCR) heavy (H) chain alone is sufficient for confident identification of clonal relationships.
• While inconsistencies exist, H chain information provides a robust basis for clonal inference in adaptive immunity studies.
• Further leveraging H chain sequence data may offer avenues for refining clonal relationship identification.