Instead, only one segment of V, D, and J can be selected to form a particular exon to finish BCR assembly under physiological and pathological conditions. Clearly, B cells can never take full advantage of all V, D, and J segments. V composes of 44 segments, 25 for D and 6 for J to encode IgH ( Li et al., 2004). There are multiple open reading frames (ORFs) in V, D, and J sequence. The variable (V), diversity (D), and joining (J) segments locus on the long arm (q) of chromosome 14 perform gene arrangements to form a specific exon of IgH, and simultaneously the V and J segments locus on the short arm (p) of chromosome 2 (for Igκ) and 22 (Igγ) perform gene arrangements to generate IgL. Somatic recombination or V(D)J recombination (VDJ recombination for IgH and VJ recombination for IgL) is the basis of BCR repertoire diversification. Notably, the variable region is the basis of antigen binding and adaptative immune defenses. The general structure of BCR has been summarized in Figure 1. IgH and IgL comprise a constant region and variable region, and three constant regions are included in IgH and one in IgL, which determines the species of produced Igs and coupled Igκ or Igγ of IgL with IgH, respectively. The IgH and IgL of BCRs are produced in sequence, controlled by sequential gene rearrangements, at subsequent cellular stages of lymphocyte development ( Melchers, 2005). In this section, we primarily introduce the structure and variety of human BCR repertoires and emphasize its major functions in fighting against exogenous or pathogenic stimuli.īCRs constitute important mediators in adaptive immune responses, and they are heterodimers composed of two immunoglobulin light chains (IgLs) and two immunoglobulin heavy chains (IgHs) ( Minervina et al., 2019). BCR sequencing has raised our awareness of the diversity and dynamics of BCR repertoires, offering novel insights into the development of diagnostic and therapeutic strategies in immune-mediated diseases. The diversification of BCR is formed by frequent somatic changes of germline DNA, which generates unique sequences and facilitates our body’s defense against all different kinds of antigens ( Nielsen and Boyd, 2018). With the advent of bioinformatics and the development of a variety of bioinformatics analysis tools, we have grasped a more comprehensive understanding of diseases, and meanwhile, disease diagnosis and treatment have become increasingly diversified ( Liu et al., 2021).ī cell receptor assembly and repertoire diversificationīCRs are composed of membrane-bound immunoglobulins that can identify and bind to specific antigens ( Hoehn et al., 2016). In recent years, BCR repertoire sequencing has been reported to be applied to dozens of immune-mediated diseases, especially in systemic lupus erythematosus (SLE) ( Bashford-Rogers et al., 2019 Liu et al., 2017 Zheng et al., 2021), COVID-19 ( Bieberich et al., 2021 Galson et al., 2020 Jin et al., 2021 Montague et al., 2021 Niu et al., 2020 Paschold et al., 2021 Schultheiβ et al., 2020 Xiang et al., 2022 Zhang et al., 2020a, 2022 Zhou et al., 2021) and vaccination ( Lee et al., 2016a Miyasaka et al., 2019 Schneikart et al., 2020 Strauli and Hernandez, 2016 Zhao et al., 2021a, 2021b). Advances in high-throughput sequencing continue to improve our understanding of diseases, especially in the application of BCR repertoire ( Yaari and Kleinstein, 2015). BCR has three complementarity determining regions (CDRs), namely CDR1, CDR2, and CDR3, among which diversity mainly arises from complementarity determining region 3 (CDR3) ( Pineda et al., 2019). The tremendous variation of BCRs is generated through the rearrangement of variable (V), diversity (D), and joining (J) genes. In order to recognize a wide variety of antigens from the outside world, individuals must generate a large number of B cell receptors (BCRs).
0 Comments
Leave a Reply. |