The production of immunoglobulin A (IgA) in mammals exceeds all other isotypes, and it is mostly exported across mucous membranes. The discovery of IgA and the realization that it dominates humoral mucosal immunity, in contrast to the IgG dominance of the systemic immune system, was early evidence for the distinct nature of mucosal immunology. It is now clear that IgA can function in high-affinity modes for neutralization of toxins and pathogenic microbes, and as a low-affinity system to contain the dense commensal microbiota within the intestinal lumen. The basic map of induction of IgA B cells in the Peyer's patches, which then circulate through the lymph and bloodstream to seed the mucosa with precursors of plasma cells that produce dimeric IgA for export through the intestinal epithelium, has been known for more than 30 years. In this review, we discuss the mechanisms underlying selective IgA induction of mucosal B cells for IgA production and the immune geography of their homing characteristics. We also review the functionality of secretory IgA directed against both commensal organisms and pathogens.

IgA class switching is the process whereby B cells acquire the expression of IgA, the most abundant antibody isotype in mucosal secretions. IgA class switching occurs via both T-cell-dependent and T-cell-independent pathways, and the antibody targets both pathogenic and commensal microorganisms. This Review describes recent advances indicating that innate immune recognition of microbial signatures at the epithelial-cell barrier is central to the selective induction of mucosal IgA class switching. In addition, the mechanisms of IgA class switching at follicular and extrafollicular sites within the mucosal environment are summarized. A better understanding of these mechanisms may help in the development of more effective mucosal vaccines.

The gut mucosa is exposed to a large community of commensal bacteria that are required for the processing of nutrients and the education of the local immune system. Conversely, the gut immune system generates innate and adaptive responses that shape the composition of the local microbiota. One striking feature of intestinal adaptive immunity is its ability to generate massive amounts of noninflammatory immunoglobulin A (IgA) antibodies through multiple follicular and extrafollicular pathways that operate in the presence or absence of cognate T-B cell interactions. Here we discuss the role of intestinal IgA in host-commensal mutualism, immune protection, and tolerance and summarize recent advances on the role of innate immune cells in intestinal IgA production.

Immunoglobulin A is the most abundant immunoglobulin isotype in mucosal secretions. In this review, we summarize recent advances in our understanding of the sites, mechanisms and functions of intestinal IgA synthesis in mice. On the basis of these recent findings, we propose an updated model for the induction and regulation of IgA responses in the gut. In addition, we discuss new insights into the role of IgA in the maintenance of gut homeostasis and into the reciprocal interactions between gut B cells and the bacterial flora.

Most antibody-secreting cells (ASCs) in mucosal tissues produce immunoglobulin A (IgA), the most abundant immunoglobulin in the body and the main class of antibody found in secretions. IgA-ASCs differentiate in the mucosal-associated lymphoid tissues and are usually considered as a homogeneous population of cells. However, IgA-ASCs that travel to the small intestine have unique characteristics in terms of their migratory requirements. These IgA-ASCs require the homing molecules alpha4beta7 and CCR9 to interact with their ligands, mucosal addressin cell adhesion molecule-1 and CCL25, which are constitutively expressed in the small intestine. Indeed, recent work has shown that IgA-ASCs specific for the small bowel are generated under different conditions as compared with IgA-ASCs in other mucosal compartments. Moreover, the mechanisms inducing IgA class switching may also vary according to the tissue where IgA-ASCs differentiate. Here we describe the mechanisms involved in the differentiation of IgA-ASCs in mucosal compartments, in particular those involved in the generation of gut-homing IgA-ASCs.

An important activity of mucosal surfaces is the production of Ab referred to as secretory IgA (SIgA). SIgA serves as the first line of defense against microorganisms through a mechanism called immune exclusion. In addition, SIgA adheres selectively to M cells in intestinal Peyer's patches, thus mediating the transepithelial transport of the Ab molecule from the intestinal lumen to underlying gut-associated organized lymphoid tissue. In Peyer's patches, SIgA binds and is internalized by dendritic cells in the subepithelial dome region. When used as carrier for Ags in oral immunization, SIgA induces mucosal and systemic responses associated with production of anti-inflammatory cytokines and limits activation of dendritic cells. In terms of humoral immunity at mucosal surfaces, SIgA appears thus to combine properties of a neutralizing agent (immune exclusion) and of a mucosal immunopotentiator inducing effector immune responses in a noninflammatory context favorable to preserve local homeostasis of the gastrointestinal tract.

In mammals, the gut is populated with an extremely dense and diverse bacterial community. One response following intestinal colonization is the production of immunoglobulin (Ig) A by B cells present in the gut-associated lymphoid tissues (GALT). In this review, we summarize recent advances in our understanding of the sites, mechanisms, and functions of intestinal IgA synthesis. We discuss here the pathways leading to IgA production, in organized structures as well as nonorganized tissues, by T-dependent as well as T-independent mechanisms. In addition, we discuss new insights into the role of gut IgA in the regulation of bacterial communities and maintenance of immune homeostasis.

Our intestine is colonized by an impressive community of bacteria, that has profound effects on the immune functions. The relationship between gut microbiota and the immune system is one of reciprocity: bacteria have important contribution in nutrient processing and education of the immune system and conversely, the immune system, particularly gut-associated lymphoid tissues (GALT) plays a key role in shaping the repertoire of gut microbiota. In this review we discuss new insights into the role of IgA in the maintenance of immune homeostasis and the reciprocal interactions between gut B cells and intestinal bacteria.

The gastrointestinal tract is colonized by an immense number of bacteria that are in a constant dialog with our immune cells. One obvious question is how the mucosal immune system maintains a state of hypo-responsiveness toward the commensal bacteria and a state of readiness that allows efficient and prompt responses against pathogens. The answers have important implications for immunologists who seek to understand the fundamental aspects of bacteria-immune cell interactions in the steady-state condition and wish to elucidate the patho-physiologic mechanisms in immune disregulations, such as inflammatory bowel diseases. An important adjustment of the immune system to bacterial colonization of the gut is the "constitutive" production of IgA by the gut-associated lymphoid tissues (GALT). In this review, we summarize the sites and mechanisms for IgA synthesis in mice. We emphasize the important role played by secretory IgAs in maintenance of an appropriate intestinal microbiota, which is required for local and systemic immune homeostasis.

The mucosal immune system acts as a first line of defense against bacterial and viral infections while also playing a crucial role in the establishment and maintenance of mucosal homeostasis between the host and the outside environment. In addition to epithelial cells and antigen-presenting cells (dendritic cells and macrophages), B and T lymphocytes form a dynamic mucosal network for the induction and regulation of secretory IgA (S-IgA) and cytotoxic T lymphocyte (CTL) responses. This review seeks to shed light on the pathways of induction and regulation of these responses and to elucidate the role they simultaneously play in fending off pathogen invasion and maintaining mucosal homeostasis.