Other studies used lineage trees to describe this mutation–selection process. Considerable attention has also been given to quantifying hypermutations and disentangling them from site specific selection, either by comparing synonymous and non-synonymous mutations, or functional and non-functional rearrangements. A number of studies have characterized the effects of B-cell selection, reporting length reduction and selection against hydrophobicity as dominant features. Gene usage was studied by both immunoscope techniques and single-cell PCR, and the variable length distributions of the complementarity-determining region 3 (CDR3) were reported. Many characteristics of B-cell repertoires have previously been described using a variety of methods. Here, we also introduce a new probabilistic model to describe hypermutations (specific to B cells), as well as new tools to automatically detect and assign new V, D and J alleles in individuals from their repertoire data, and to infer the distribution of these alleles among their two chromosomes.
Some of these techniques were developed in to describe T-cell repertoires. We work with large samples of human BCR heavy chain DNA sequence 1 and apply advanced statistical techniques to accurately quantify the processes that shape B-cell repertoire diversity-generation, selection and hypermutations. Recent advances in sequencing technologies make it possible to obtain copious data on immune cell receptor sequences. Apart from the possibility of hypermutations, the generation and selection processes are very similar in B and T cells, and involve common enzymes and pathways. These hypermutations are selected for antigen binding through the process of affinity maturation. Additionally, unlike T cells, BCR sequences are subject to point hypermutations during the proliferation that follows successful recognition of an antigen. Later, they undergo further selection depending on their ability to recognize foreign antigen. Before these cells leave for the periphery, they are initially selected for functionality. These receptors are formed during the VDJ recombination process in the bone marrow. The diversity of the B-cell repertoire is encoded in the different amino acid composition of B-cell receptors (BCRs) expressed on the surface of these cells. Along with T cells, B cells contribute to the large diversity of immune cells that specifically recognize antigens.
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