Three different forms of IgA exist:
- Monomeric IgA: present in the blood up to 3g/L. It protects the mucous membranes from infection and activates local lymphoid organs to prevent an infection from spreading1.
- Dimeric IgA: present in the mucous membrane. It has the same function as monomeric IgA but with a higher avidity and the possibility of being secreted as secretory IgA11.
- Secretory IgA: present in the lumen of mucosal organs. It neutralizes infections directly in the lumen of organs by recognition, agglutination and immune exclusion1.
1 Stubbe and Corthesy, 2000. J. Immunol
An example: the secretory IgA
A. Production of secretory IgA (sIgA)
Although monomeric IgA is predominantly concentrated in blood produced by bone marrow plasma cells, dimeric IgA is preferentially expressed in the lamina propria. This dimerization requires a 15-kDa joining (J) chain covalently bound to the tailpiece of two IgA. The J chain in the IgA dimer is critical for its transport onto mucosal surfaces, because it mediates the recognition through the polymeric Ig receptor (pIgR) on the basolateral surface of the epithelial cells allowing the IgA binding (Johansen, F. E., R. Braathen, P. Brandtzaeg. 2001. The J chain is essential for the polymeric Ig receptor-mediated epithelial transport of IgA. J. Immunol. 167: 5185–5192). After endocytotic internalization and transcytosis, pIgR is cleaved at the luminal surface and the extracellular loop of the receptor remains covalently linked to the dimer, releasing secretory IgA.
B. SIgA interactions : immun complexes
Immune complexes (containing a sIgA and its target) formed in the lumen of the body, can be actively redirected to the lamina propria by active retrograde transport, and be addressed to macrophages or dendritic cells leading to the enzymatic digestion of the target and its presentation by the class II histocompatibility complex, contributing to local immune system homeostasis. This feature of the sIgA, called reverse transcytosis, is mediated by M epithelial cells via two recently-identified receptors, Dectin-1 and Siglec 5 (Rochereau et al., 2013, Plos Biology vol11) to address the DC, or sub-epithelial mucous dendritic cells directly via the DC-SIGN receptor (Baumann et al., 2010, Immunol letter, June 15; 131).
C. SIgA functions
Interactions between epithelium and commensal bacteria in the digestive tube are not well known. However, it has been shown that an association between a Lactobacillus rhamnosus and a SIgA increases the adherence of probiotics on the epithelium surface.
Several data give clues to the functions of SIgA. These may be divided into two main functions::
- Immune exclusion: SIgA helps to regulate the mucous environment by acting on epithelial cells responses. In addition, immune complexes in association with the epithelium are thought to regulate the level of colonization of the gut.
- Immune inclusion: this function is still the subject of debate. The hypothesis would be that SIgA are involved in the formation of the biofilm that improves the environment for bacterial growth
Secretory IgA (SIgA) are closely linked to bacteria colonization. SIgA play a critical role in the regulation of the microbial flora. Mucosal immune imbalance may open the way to infection.