b Alignment-free detection of reads containing full-length CDR3s and simultaneously overlapping V and J genes. Complementarity-determining region 3 (CDR3) is used to identify Ig receptor clonotypes-a group of clones with identical CDR3 amino acid sequences. Reads with extensive somatic hypermutations and reads spanning the V(D)J recombination are inferred from the unmapped reads (gray color). Reads entirely aligned to Ig genes are inferred from mapped reads (black color). V(D)J gene segments are randomly joined and non-templated bases (N, dark red color) are inserted at the recombination junctions. Ig receptors contain multiple variables (V, green color), diversity (D, which is present only in IGH, violet color), joining (J, yellow color), and constant (C, blue color) gene segments. Ig repertoire consists of three Ig loci: immunoglobulin heavy locus (IGH), immunoglobulin κ locus (IGK), and immunoglobulin λ locus (IGL). The pairing of heavy and light chains that occurs in polyclonally activated B cells chains is another mechanism that increases Ig diversity.Ī Schematic representation of human Ig receptor repertoire. Here, antigen specificity remains unchanged, while the heavy chain VDJ regions join with different constant (C) regions, such as IgG, IgA, or IgE isotypes, and alter the immunological properties of Igs. Isotype switching is another mechanism that contributes to B-cell functional diversity. These changes are mostly single-base substitutions occurring at extremely high rates-somatic hypermutation can undergo 10 −5 to 10 −3 mutations per base pair per generation 3. In addition, upon activation of a B cell, somatic hypermutation further diversifies Ig in their variable region. Ig repertoire diversity is key for an individual’s immune system to confer protection against a wide variety of potential pathogens 2. This process enables the Ig repertoire to develop astonishing diversity of antigen receptors from any given individual, with >10 13 theoretically possible distinct Ig receptors 1. The resulting DNA sequences are then translated into antigen receptor proteins. Igs are diversified through somatic recombination, a process that randomly combines variable (V), diversity (D), and joining (J) gene segments, and inserts or deletes non-templated bases at the recombination junctions 1 (Fig. A typical Ig repertoire is composed of one immunoglobulin heavy chain (IGH) and two light chains, κ (IGK) and λ (IGL). B cells recognize their specific antigens through immunoglobulins (Ig), surface antigen receptors, which are unique to each cell and its progeny. A key function of the adaptive immune system is to mount protective memory responses to a given antigen.
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