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

Abstract

Key Points More than 80% of H chain–based clones contained cells expressing consistent L chains. L chain junction diversity did not further refine these H chain–based clones. Leveraging additional H chain features could improve B cell clonal inference. B cell clonal expansion is vital for adaptive immunity. High-throughput BCR sequencing enables investigating this process but requires computational inference to identify clonal relationships. This inference usually relies on only the BCR H chain, as most current protocols do not preserve H:L chain pairing. The extent to which paired L chains aids inference is unknown. Using human single-cell paired BCR datasets, we assessed the ability of H chain–based clonal clustering to identify clones. Of the expanded clones identified, <20% grouped cells expressing inconsistent L chains. H chains from these misclustered clones contained more distant junction sequences and shared fewer V segment mutations than the accurate clones. This suggests that additional H chain information could be leveraged to refine clonal relationships. Conversely, L chains were insufficient to refine H chain–based clonal clusters. Overall, the BCR H chain alone is sufficient to identify clonal relationships with confidence.