The immune geography of IgA induction and function

The immune geography of IgA induction and function

VOLUME 1 NUMBER 1 | JANUARY 2008 | AJ Macpherson1, KD McCoy1, F-E Johansen2 and P Brandtzaeg2
The production of immunoglobulin A (IgA) is the most abundant isotype in mammals and is primarily secreted across mucous membranes. The discovery of IgA and its dominance in mucosal immunity, in contrast to the dominance of IgG in systemic immunity, highlighted the distinct nature of mucosal immunology. IgA functions in both high-affinity modes for neutralizing toxins and pathogens and in low-affinity systems to contain the dense commensal microbiota in the intestinal lumen. The induction of IgA-secreting B cells in Peyer's patches and their homing to the mucosa to seed plasma cells producing dimeric IgA for export through the intestinal epithelium have been well-studied for over 30 years. This review discusses the mechanisms underlying the selective induction of IgA-secreting B cells and their homing characteristics, as well as the functionality of secretory IgA against both commensal organisms and pathogens. The role of commensal intestinal microbes in inducing IgA production and the mechanisms of IgA neutralization of pathogens and exotoxins are also reviewed. Additionally, the review explores the class switch recombination of IgA and the role of costimulatory signals such as BAFF and APRIL in IgA production. The immune geography of IgA induction and function, including the contributions of different tissue sites and B cell subsets, is discussed, emphasizing the unique immune system at mucosal surfaces. Finally, the protective mechanisms of IgA against non-pathogens and microbial pathogens are examined, highlighting the redundancy and complexity of mucosal immunity.The production of immunoglobulin A (IgA) is the most abundant isotype in mammals and is primarily secreted across mucous membranes. The discovery of IgA and its dominance in mucosal immunity, in contrast to the dominance of IgG in systemic immunity, highlighted the distinct nature of mucosal immunology. IgA functions in both high-affinity modes for neutralizing toxins and pathogens and in low-affinity systems to contain the dense commensal microbiota in the intestinal lumen. The induction of IgA-secreting B cells in Peyer's patches and their homing to the mucosa to seed plasma cells producing dimeric IgA for export through the intestinal epithelium have been well-studied for over 30 years. This review discusses the mechanisms underlying the selective induction of IgA-secreting B cells and their homing characteristics, as well as the functionality of secretory IgA against both commensal organisms and pathogens. The role of commensal intestinal microbes in inducing IgA production and the mechanisms of IgA neutralization of pathogens and exotoxins are also reviewed. Additionally, the review explores the class switch recombination of IgA and the role of costimulatory signals such as BAFF and APRIL in IgA production. The immune geography of IgA induction and function, including the contributions of different tissue sites and B cell subsets, is discussed, emphasizing the unique immune system at mucosal surfaces. Finally, the protective mechanisms of IgA against non-pathogens and microbial pathogens are examined, highlighting the redundancy and complexity of mucosal immunity.
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Understanding The immune geography of IgA induction and function