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 7 days 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 21 days 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.

Original publication

DOI

10.1016/j.ebiom.2015.11.034

Type

Journal

EBioMedicine

Publication Date

12/2015

Volume

2

Pages

2070 - 2079

Keywords

B cell repertoire, Immunoglobulin repertoire, Vaccination, mAbs, Adult, Antibody Specificity, B-Lymphocyte Subsets, Computational Biology, Databases, Genetic, Hepatitis B, Hepatitis B Antibodies, Hepatitis B Vaccines, Hepatitis B virus, High-Throughput Nucleotide Sequencing, Humans, Immunoglobulin Isotypes, Immunologic Memory, Lymphocyte Count, Middle Aged, Plasma Cells, Sequence Analysis, DNA, Time Factors, Vaccination, Young Adult