12/15/2023 0 Comments Antibody repertoireThe authors performed multiple analyses on the same tonsil samples, including deep bulk repertoire sequencing (obtaining up to hundreds of thousands of immunoglobulin sequences) along with scRNA-seq including Ig region VDJ sequencing. Integrated bulk and single-cell repertoire analysis improves mapping of B cell responses.This offers a very rich dataset for understanding of human B cell dynamics and maturation through the memory B cell compartment, as well as insights into the timing and effects of CSR and SHM. In this preprint, King et al undertake a deep investigation of human B cells from the tonsils, a secondary lymphoid organ containing germinal centers as well as naïve B cells. The precise coordination of these two processes with commitment to memory or PC lineages is an open area of investigation. CSR involves excision of components of the immunoglobulin gene locus from the genome, which changes the constant region of the resulting antibody and endows the antibody with its effector potential – such as the complement-activating potential of some IgG subclasses or the dimerization of particular IgAs. SHM involves the random mutation of the gene, which is then selected for improved affinity towards the antigen in a complex process dependent on help from T cells and occurring in a spatially defined pattern in the GC. SHM and CSR are two distinct processes that alter the potential function of an antibody through modification of the encoding immunoglobulin gene. Through a process largely coordinated in and around a special structure known as a germinal center (GC), B cells modify their genome through the processes of somatic hypermutation (SHM) and class switch recombination (CSR), and differentiate into several lineages, including long-lived memory B cells and plasma cells (PCs). Upon exposure to an antigen challenge, B cells undergo three main processes which underly the efficacy and long-term potential of antibody responses. The production of antibodies by B cells is a key feature of adaptive immunity, is often critical for long-lasting protection from re-infection, and underlies the protective effect of most vaccine strategies.
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