Abstract
The vast diversity of B-cell receptors (BCR) and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.
Highlights
The diverse B-cell repertoire of a healthy individual allows the recognition of a wide range of antigenic epitopes, resulting in a robust adaptive humoral immune response against pathogens
CD19+ B cells comprise 7–11% of lymphocytes circulating in peripheral blood[45]
This population is dominated by naive B cells, which correspond roughly to 65% of all peripheral B cells, while memory B cells account for about 30% of all circulating B cells[45]
Summary
The diverse B-cell repertoire of a healthy individual allows the recognition of a wide range of antigenic epitopes, resulting in a robust adaptive humoral immune response against pathogens. The human immunoglobulin heavy chain (IgH) locus comprises approximately one megabase of chromosome 14, and contains at least 51 functional variable (V) region genes, 25 diversity (D) genes and 6 joining (J) genes that undergo a series of recombination events to assemble a functional heavy chain[1,2,3]. This recombination process creates a vast array of antigen-binding receptors through the random assortment of different V, D, and J segments (combinatorial diversity), and the insertion of non-templated (N) and palindromic nucleotides (P) at the junctions between V/D and D/J segments (junctional diversity). The human immunoglobulin light chain к and λ loci occupy approximately one megabase on chromosomes 2 and 22, respectively, and contain 30–40 V and 4–5 J
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