Secretory Immunoglobulin A


Secretory immunoglobulin A (IgA) (SIgA) is the most abundant Ig produced at the surface of mucosal membranes in mammals. These very thin and sensitive barriers are challenged by occasional pathogenic microbes as well as by permanently residing commensal bacteria. Although not the unique guardian of mucosal epithelia, SIgA is an important component of the protective function guaranteeing maintenance of homoeostasis and wellness. Topics presented in this article include: (1) mechanisms involved in local induction of SIgA via T‐cell‐dependent and ‐independent pathways; (2) structure–function relationship in SIgA; (3) immunoregulatory role of SIgA vis‐à‐vis pathogens and commensals and (4) the unexpected contribution of SIgA in diseases. Because this is the most studied mucosal environment, most of the functional characteristics of SIgA are exemplified with respect to the gastrointestinal tract.

Key Concepts:

  • SIgA is the most abundant immunoglobulin produced at mucosal surfaces, and it exists in secretions in polymeric forms of high and low antigenic affinity/avidity.

  • The presence of secretory component in SIgA confers additional features including improved stability, proper anchoring in mucus and adequate localisation for optimal functions on the antibody.

  • Because epithelia in the gastrointestinal, respiratory and urogenital tracts are highly sensitive to invading environmental antigens, shielding of mucosal surfaces by SIgA is crucial to the process of protection and homoeostasis.

  • In addition to canonical immune exclusion, SIgA is endowed with the capacity to transport immune complexes via M‐cells to underlying dendritic cells, thus inducing attenuated mucosal and systemic immune responses.

  • Communication between natural polyreactive SIgA‐commensal bacteria complexes and the epithelial cells lining mucosal surfaces contributes to regulate the symbiotic host–commensal relationship.

  • SC, by itself, via multiple glycosylation sites, displays neutralising properties against pathogen‐associated molecules. This holds true when SC is bound to polymeric IgA in the SIgA molecule.

  • Increasing knowledge of the multiple modes of action of SIgA provides opportunities to investigate the potential of the antibody in passive immunisation against bacteria, viruses and toxins in the clinics.

Keywords: secretory IgA ; secretory component; mucosal immune responses; pathogens; commensals; dendritic cells; Peyer's patch; homoeostasis

Figure 1.

Induction of IgA production in the mouse GALT. T‐cell‐dependent IgA responses are triggered following receptor‐mediated uptake of antigens sampled by M‐cells and delivered to underlying DCs in the SED region (pathway 1) or by intra‐epithelial DCs extending their dendrites in the luminal environment (pathway 2). Subsequent activation of CD4+ T‐cells in the IFR of Peyer's patches will depend on the nature of the antigen, in particular the presence of associated danger signals. In the intestinal environment, local and epithelial cell‐derived conditioning (TGF‐β, thymic stromal lymphopoietin and retinoic acid (RA)) prompt DCs to differentiate T‐cells into dominating Th2 and Treg populations producing IL‐4, IL‐5, IL‐6, IL‐10 and TGF‐β, a bunch of cytokines important to the process of class switch recombination taking place after CD40L–CD40 cross‐linking between T‐ and B‐cells (pathway 3). Further differentiation of some regulatory T (Treg) cells into TFH contributes to CSR as well (pathway 3). In the Peyer's patch, inducible nitric oxide synthase (iNOS)+TNF‐α+ DCs enhances CSR and production by upregulating the expression of the TGF‐β receptor on B‐cells via nitric oxide (NO) (pathway 4). On the influence of local RA, switched IgA+ B‐cells upregulate the surface markers α4β7 integrin and CCR9 chemokine receptor and migrate via the thoracic duct to proximal and distant mucosal sites where they terminally differentiate into plasma cells producing polymeric IgA (pIgA) (pathway 5). It is generally accepted that this T‐cell‐dependent pathway eventually generates high‐affinity IgA antibodies with a unique specificity that in secretions recognise pathogenic microbes and protein toxins. On TLR‐mediated sensing of bacteria, follicular DC in the Peyer's patch directly educate B‐cells to switch to IgA production, a mechanism that is independent of the canonical T–B cell interaction but requires the B‐cell‐activating factor of the TNF family BAFF, a proliferation‐inducing ligand (APRIL), and TGF‐β (pathway 6). Together with NO and IL‐6 released by intestinal epithelial cells, the same CSR factors secreted by lamina propria DCs having detected bacteria via TLRs contribute to T‐cell‐independent activation (pathway 7) of mostly peritoneal B1 cells prone to secrete low‐affinity, multireactive IgA antibodies involved in the control of the commensal microbiota.

Figure 2.

Schematic representation of the structure and the secretion pathway of SIgA. (a) Although structures of higher degree of polymerisation have been recovered in secretions, SIgA exists mostly as a dimer. Two IgA monomers containing canonical heavy and light chains with domains depicted in purple are linked together by the joining (J) chain (red) in a tail‐to‐tail arrangement. SC (green) comprises five Ig‐like domains and is covalently bound to the Fc portion of polymeric IgA (pIgA). IgA and SC display several glycosylation sites drawn for simplification as yellow spheres on half a monomer. (b) Once produced by plasma cells in the lamina propria, pIgA interacts with the pIgR in a J chain‐dependent manner and is transported through epithelial cells from the basal to the apical side, a mechanism referred to as transcytosis. Migration along successive intracellular compartments (ARE, apical recycling endosome; BEE, basolateral early endosome; CE, common endosome) ensures controlled basolateral to apical move of the antibody–pIgR complex. Following apical cleavage of pIgR, SIgA is released into the lumen in the form of SIgA, a complex made of pIgA and bound SC.

Figure 3.

Protective and immunomodulatory functions of SIgA. The multifaceted modes of action of SIgA are depicted. Although immune exclusion remains the primordial function of SIgA in the intestinal mucosae, the antibody is involved in several processes that participate in the maintenance of local homoeostasis vis‐à‐vis pathogenic and commensal bacteria. Many cellular and molecular immune and nonimmune partners are involved in the communication between SIgA and the epithelium, eventually ensuring the integrity of this fragile barrier.



Benckert J , Schmolka N , Kreschel C et al. (2011) The majority of intestinal IgA+ and IgG+ plasmablasts in the human gut are antigen‐specific. Journal of Clinical Investigation 121: 1946–1955.

Bonner A , Almogren A , Furtado PB , Kerr MA and Perkind SJ (2009) The nonplanar secretory IgA2 and near planar secretory IgA1 solution structures rationalize their different mucosal immune responses. Journal of Biological Chemistry 284: 5077–5087.

Bonner A , Perrier C , Corthésy B and Perkins SJ (2007) Solution structure of human secretory component and implications for biological function. Journal of Biological Chemistry 282: 16969–16980.

Boullier S , Tanguy M , Kadaoui K et al. (2009) Secretory IgA‐mediated neutralization of Shigella flexneri prevents intestinal tissue destruction by down‐regulating inflammatory circuits. Journal of Immunology 183: 5879–5885.

Brandtzaeg P and Johansen FE (2005) Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties. Immunological Reviews 206: 32–63.

Brandtzaeg P and Pabst R (2004) Let's go mucosal: communication on slippery ground. Trends in Immunology 25: 570–577.

Cao AT , Yao S , Gong B , Elson CO and Cong Y (2012) Th17 cells upregulate polymeric Ig receptor and intestinal IgA and contribute to intestinal homeostasis. Journal of Immunology 189: 4666–4673.

Cerutti A (2008) The regulation of IgA class switching. Nature Reviews Immunology 8: 421–434.

Corr SC , Gahan CC and Hill C (2008) M‐cells: origin, morphology and role in mucosal immunity and microbial pathogenesis. FEMS Immunology and Medical Microbiology 52: 2–12.

Corthésy B (2007) Roundtrip ticket for secretory IgA: role in mucosal homeostasis? Journal of Immunology 178: 27–32.

Corthésy B (2010) Role of secretory immunoglobulin A and secretory component in the protection of mucosal surfaces. Future Microbiology 5: 817–829.

Deplanke B and Gaskins HR (2001) Microbial modulation of innate defense: goblet cells and the intestinal mucus layer. American Journal of Clinical Nutrition 73: 1131S–1141S.

Favre L , Spertini F and Corthésy B (2005) Secretory IgA possesses intrinsic modulatory properties stimulating mucosal and systemic immune responses. Journal of Immunology 175: 2793–2800.

Fries PN and Griebel PJ (2011) Mucosal dendritic cell diversity in the gastrointestinal tract. Cell Tissue Research 343: 33–41.

Hase K , Kawano K , Nochi T et al. (2009) Uptake through glycoprotein 2 of FimH+ bacteria by M cells initiates mucosal immune responses. Nature 462: 226–230.

Jaffar Z , Ferrini ME , Herritt LA and Roberts K (2011) Lung mucosal Th17‐mediated responses induce polymeric Ig receptor expression by the airway epithelium and elevate secretory IgA levels. Journal of Immunology 182: 4507–4511.

Johansen FE , Braathen R and Brandtzaeg P (2000) Role of J chain in secretory immunoglobulin formation. Scandinavian Journal of Immunology 52: 240–248.

Kadaoui KA and Corthésy B (2007) Secretory IgA mediates bacterial translocation to dendritic cells in mouse Peyer's patches with restriction to mucosal compartment. Journal of Immunology 179: 7751–7757.

Kaetzel CS (2005) The polymeric immunoglobulin receptor: bridging innate and adaptive immune responses at mucosal surfaces. Immunological Reviews 206: 83–99.

Kiyono H and Fukuyama S (2004) NALT‐ versus Peyer's patch‐ mediated mucosal immunity. Nature Reviews Immunology 4: 699–710.

Macpherson AJ , Geuking MB and McCoy KD (2012) Homeland security: IgA at the frontier of the body. Trends in Immunology 33: 160–167.

Macpherson AJ , McCoy KD , Johansen FE and Brandtzaeg P (2008) The immune geography of IgA induction and function. Mucosal Immunology 1: 11–22.

Mantis NJ , Cheung MC , Chintalacharuvu KR et al. (2002) Selective adherence of IgA to murine Peyer's patch M cells: evidence for a novel IgA receptor. Journal of Immunology 169: 1844–1851.

Mantis NJ and Forbes SJ (2010) Secretory IgA: arresting microbial pathogens at epithelial borders. Immunological Investigations 39: 383–406.

Mantis NJ , Rol N and Corthésy B (2011) Diverse regulatory pathways for IgA synthesis in the gut. Mucosal Immunology 4: 468–471.

Mathias A and Corthésy B (2011) Recognition of Gram‐positive intestinal bacteria by hybridoma‐ and colostrum‐derived secretory immunoglobulin A Is mediated by carbohydrates. Journal of Biological Chemistry 286: 17239–17247.

Mathias A , Duc M , Favre L et al. (2010) Potentiation of polarized intestinal Caco‐2 cell responsiveness to probiotics complexed with secretory IgA. Journal of Biological Chemistry 285: 33906–33913.

Matysiak‐Budnik T , Moura IC , Arcos‐Fajardo M et al. (2008) Secretory IgA mediates retrotranscytosis of intact gliadin peptides via the transferrin receptor in celiac disease. Journal of Experimental Medicine 205: 143–154.

Mestecky J and Russell MW (2009) Specific antibody activity, glycan heterogeneity and polyreactivity contribute to the protective activity of S‐IgA at mucosal surfaces. Immunological Letters 124: 57–62.

Mestecky J , Russell MW and Elson CO (1999). Intestinal IgA: novel views on its function in the defence of the largest mucosal surface. Gut 44: 2–5.

Monteiro R and van de Winkel JG (2003) IgA Fc receptors. Annual Review of Immunology 21: 177–204.

Mora JR and von Andrian UH (2009) Role of retinoic acid in the imprinting of gut‐homing IgA‐secreting cells. Seminars in Immunology 21: 22–27.

Newberry RD (2008) Intestinal lymphoid tissues: is variety an asset or a liability? Current Opinion in Gastroenterology 24: 121–128.

Niedergang F and Kraehenbuhl JP (2000) Much ado M cells. Trends in Cell Biology 10: 137–141.

Ogra PL , Mestecky J , Lamm ME et al. (2005) Mucosal Immunology, 3rd edn. San Diego: Academic Press.

Perrier C and Corthésy B (2010) Gut permeability and food allegies. Clinical and Experimental Allergy 41: 20–28.

Peterson DA , McNulty NP , Guruge JL and Gordon JI (2007) IgA response to symbiotic bacteria as a mediator of gut homeostasis. Cell Host Microbe 2: 328–339.

Phalipon A and Corthésy B (2003) Novel functions of the polymeric Ig receptor: well beyond transport of immunoglobulins. Trends in Immunology 24: 55–58.

Pilette C , Durham SR , Vaerman JP and Sibille Y (2004) Mucosal immunity in asthma and chronic obstructive pulmonary disease. Proceedings of the American Thoracic Society 1: 125–135.

Rescigno M , Lopatin U and Chieppa M (2008) Interactions among dendritic cells, macrophages and epithelial cells in the gut: implication for immune tolerance. Current Opinion in Immunology 20: 669–675.

Rey J , Garin N , Spertini F and Corthésy B (2004) Targeting of secretory IgA to Peyer's patch dendritic and T cells after transport by intestinal M cells. Journal of Immunology 172: 3026–3033.

Rindisbacher L , Cottet S , Wittek R , Krahenbuhl JP and Corthésy B (1995) Production of human secretory component with dimeric IgA binding capacity using viral expression systems. Journal of Biological Chemistry 270: 14220–14228.

Rol N , Favre L , Benyacoub J and Corthésy B (2012) The role of secretory IgA in the natural sensing of commensal bacteria by mouse Peyer's patch dendritic cells. Journal of Biological Chemistry 287: 40074–40082

Soloff AC and Barratt‐Boyes SM (2010) Enemy at the gates: dendritic cells and immunity to mucosal pathogens. Cell Research 20: 872–885.

Strugnell RA and Wijburg OL (2010) The role of secretory antibodies in infection immunity. Nature Reviews Microbiology 8: 656–667.

Suzuki K and Fagarasan S (2009) Diverse regulatory pathways for IgA synthesis in the gut. Mucosal Immunology 2: 468–471.

Suzuki K , Maruya M , Kawamoto S et al. (2010) The sensing of environmental stimuli by follicular dendritic cells promotes immunoglobulin A generation in the gut. Immunity 13: 73–81.

Tezuka H , Abe Y , Iwata M et al. (2007) Regulation of IgA production by naturally occurring TNF/iNOS‐producing dendritic cells. Nature 448: 929–933.

Wei M , Shinkura R , Doi Y et al. (2011) Mice carrying a knock‐in mutation of Aicda resulting in a defect in somatic hypermutation have impaired gut homeostasis and compromised mucosal defense. Nature Immunology 12: 264–270.

Woof JM and Russell MW (2011) Structure and function relationships in IgA. Mucosal Immunology 4: 590–597.

Further Reading

Bemark M , Boysen P and Lycke NY (2012) Induction of gut IgA production through T-cell dependent and T-cell independent pathways. Annals of the New York Academy of Sciences 1247: 97–116.

Brandtzaeg P (2011) The gut as communicator between environment and host: immunological consequences. European Journal of Pharmacology 668(suppl 1): S16–S32.

Cerutti A (2011) Immunoglobulin responses at the mucosal interface. Annual Review of Immunology 29: 273–293.

Pabst O (2012) New concepts in the generation and functions of IgA. Nature Review Immunology 12: 821–832.

Slack E , Balmer ML , Fritz JH and Hapfelmeier S (2012) Functional flexibility of intestinal IgA – broadening the fine lines. Frontiers in Immunology doi: 10.3389/fimmu.2012.00100.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Corthésy, Blaise(Sep 2013) Secretory Immunoglobulin A. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0024227]