[HTML][HTML] Analysis of B cell repertoire dynamics following hepatitis B vaccination in humans, and enrichment of vaccine-specific antibody sequences
EBioMedicine, 2015•thelancet.com
Generating a diverse B cell immunoglobulin repertoire is essential for protection against
infection. The repertoire in humans can now be comprehensively measured by high-
throughput sequencing. Using hepatitis B vaccination as a model, we determined how the
total immunoglobulin sequence repertoire changes following antigen exposure in humans,
and compared this to sequences from vaccine-specific sorted cells. Clonal sequence
expansions were seen 7days after vaccination, which correlated with vaccine-specific …
infection. The repertoire in humans can now be comprehensively measured by high-
throughput sequencing. Using hepatitis B vaccination as a model, we determined how the
total immunoglobulin sequence repertoire changes following antigen exposure in humans,
and compared this to sequences from vaccine-specific sorted cells. Clonal sequence
expansions were seen 7days after vaccination, which correlated with vaccine-specific …
Abstract
Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity-determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation.
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