Polymeric IgA-secreting and mucosal homing pre-plasma cells in normal human peripheral blood (original) (raw)
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Regulation of mucosal IgA responses: lessons from primary immunodeficiencies
2011
Adaptive co-evolution of mammals and bacteria has led to the establishment of complex commensal communities on mucosal surfaces. In spite of having available a wealth of immunesensing and effector mechanisms capable of triggering inflammation in response to microbial intrusion, mucosal immune cells establish an intimate dialogue with microbes to generate a state of hyporesponsiveness against commensals and active readiness against pathogens. A key component of this homeostatic balance is IgA, a noninflammatory antibody isotype produced by mucosal B cells through class switching. This process involves activation of B cells by IgAinducing signals originating from mucosal T cells, dendritic cells, and epithelial cells. Here, we review the mechanisms by which mucosal B cells undergo IgA diversification and production and discuss how the study of primary immunodeficiencies facilitates better understanding of mucosal IgA responses in humans.
Molecular heterogeneity of human IgA antibodies during an immune response
Clinical & Experimental Immunology, 2008
Human IgA occurs in multiple molecular forms (polymeric and monomeric) and two subclasses which show differential distribution between the mucosal and circulatory compartments of the immune system. However, the molecular form and subclass of specific IgA antibodies are influenced, especially during an immune response, by the type of antigen and duration of the response as well as by the route of exposure. These considerations question previously held notions that polymeric IgA and an increased representation of the IgA2 subclass among circulating antibodies or antibodysecreting cells signify their mucosal origin. Although the functional properties of different molecular forms and subclasses of IgA antibodies are incompletely understood, it appears that there is physiological benefit in the diversity of the IgA immune system.
Journal of Clinical Investigation, 2003
The dissemination of IgA-dependent immunity between mucosal sites has important implications for mucosal immunoprotection and vaccine development. Epithelial cells in diverse gastrointestinal and nonintestinal mucosal tissues express the chemokine MEC/CCL28. Here we demonstrate that CCR10, a receptor for MEC, is selectively expressed by IgA Ab-secreting cells (large s/cIgA + CD38 hi CD19 int/-CD20-), including circulating IgA + plasmablasts and almost all IgA + plasma cells in the salivary gland, small intestine, large intestine, appendix, and tonsils. Few T cells in any mucosal tissue examined express CCR10. Moreover, tonsil IgA plasmablasts migrate to MEC, consistent with the selectivity of CCR10 expression. In contrast, CCR9, whose ligand TECK/CCL25 is predominantly restricted to the small intestine and thymus, is expressed by a fraction of IgA Ab-secreting cells and almost all T cells in the small intestine, but by only a small percentage of plasma cells and plasmablasts in other sites. These results point to a unifying role for CCR10 and its mucosal epithelial ligand MEC in the migration of circulating IgA plasmablasts and, together with other tissue-specific homing mechanisms, provides a mechanistic basis for the specific dissemination of IgA Ab-secreting cells after local immunization.
The Journal of Immunology, 2000
Peyer's patches but not mesenteric lymph nodes (MLN). In this study, we used this approach to determine the importance of Peyer's patches for induction of mucosal IgA Ab responses in the murine gastrointestinal tract. Immunohistochemical analysis revealed that LTR-Ig-treated, Peyer's patch null (PP null) mice possessed significant numbers of IgA-positive (IgA ؉ ) plasma cells in the intestinal lamina propria. Further, oral immunization of PP null mice with OVA plus cholera toxin as mucosal adjuvant resulted in Ag-specific mucosal IgA and serum IgG Ab responses. OVA-specific CD4 ؉ T cells of the Th2 type were induced in MLN and spleen of PP null mice. In contrast, when TNF and LT-␣ double knockout (TNF/LT-␣ ؊/؊ ) mice, which lack both Peyer's patches and MLN, were orally immunized with OVA plus cholera toxin, neither mucosal IgA nor serum IgG anti-OVA Abs were induced. On the other hand, LTR-Ig-and TNF receptor 55-Ig-treated normal adult mice elicited OVA-and cholera toxin B subunit-specific mucosal IgA responses, indicating that both LT-␣ and TNF/LT-␣ pathways do not contribute for class switching for IgA Ab responses. These results show that the MLN plays a more important role than had been appreciated until now for the induction of both mucosal and systemic Ab responses after oral immunization. Further, organized Peyer's patches are not a strict requirement for induction of mucosal IgA Ab responses in the gastrointestinal tract.
The immune geography of IgA induction and function
Mucosal Immunology, 2008
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.