Antibody repertoire microbiome8/4/2023 Indeed, spectratypic analyses of the mucosal antibody repertoire have provided evidence of increased oligoclonality of the mucosal IgA repertoire. In contrast to conventional germinal centers in lymph nodes and other lymphoid organs, many mucosal B cells are thought to mature using T cell-independent routes, which likely affects the diversity of the mucosal antibody repertoire. In the gut mucosa, resident plasma cells secrete almost exclusively IgA, and the presence of IgA-secreting plasma cells depends on the presence of colonizing bacteria in the gut. Much less is known about the repertoire composition of tissue-resident B cells, however. Ĭirculating B cells with diverse surface receptors (that later become secreted antibodies with the same specificity) constitute the primary humoral immune cell type responding to systemic infection, and recent work has described the human peripheral blood antibody repertoire in great detail –. Surprisingly, however, circulating memory B cell repertoires often appear very similar when compared across individuals at the level of antibody variable gene usage, suggesting the presence of a global mechanism regulating the genetic composition of the peripheral blood antibody repertoire –. Since each individual has experienced a unique set of pathogenic encounters in a unique order, it is logical to expect that each individual might possess a uniquely biased memory repertoire that reflects the enrichment of clones specific for the particular history of pathogens. In studies of the circulating antibody repertoire, pathogenic infections have been shown to induce antibody responses with biased germline antibody variable gene use, and this bias is often maintained in the post-infection memory B cell population –. Repertoire diversity is further enhanced in the memory repertoire by several affinity maturation processes including somatic hypermutation, which introduces point mutations and insertions/deletions (indels), and class-switching –. Diversity in the primary (or, naïve) B cell repertoire is accomplished by combinatorial diversity that occurs following recombination of germline variable (V), diversity (D) and joining (J) germline genes and pairing of unique heavy and light chains –. The humoral immune response produces a massively diverse repertoire of antibodies In order to respond effectively to challenge from a multitude of unfamiliar pathogens. These data suggest that mucosal immune repertoires are distinct in many ways from the systemic compartment. We also noted a large increase in frequency of both insertions and deletions in the small intestine antibody repertoire. Mucosal tissue repertoires possessed longer heavy chain complementarity determining region 3 loops than lymphoid tissue repertoires. Mutation frequency analysis of mucosal tissue repertoires revealed that they were highly mutated, with little evidence for the presence of naïve B cells, in contrast to blood. The results revealed that mucosal tissues such as stomach, intestine and lung possess unique antibody gene repertoires that differed substantially from those found in lymphoid tissues or peripheral blood. We examined the expressed antibody variable gene repertoires from 10 different human tissues using RNA samples derived from a large number of individuals. Antibodies are the key to prevention of infections at the mucosal surface, but it is currently unclear whether the B cell repertoire at mucosal surfaces reflects the dominant antibodies found in the systemic compartment or whether mucosal tissues harbor unique repertoires. Recent developments in genetic technologies allow deep analysis of the sequence diversity of immune repertoires, but little work has been reported on the architecture of immune repertoires in mucosal tissues.
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