J-chain

The J (joining) chain (reviewed by Koshland, 1975 and 1985 [124,125]) is a polypeptide chain of a molecular weight of about 15000. Unlike heavy and light chains, which contribute to all immunoglobulin molecules, the J chain is only attached covalently via disulphide bridges to the Fc portion of secreted IgM and IgA [126,127]. J chain associated with IgM or IgA shows a high affinity for the secretory component protein [128] and it is therefore believed to be necessary for rapid transport through secretory epithelial cells into exocrine fluids [129], 

Comparison of the amino acid sequence (shown in one letter code [165]) of the membrane portion of mouse IgH chains, starting with the first amino acid which distinguishes the membrane from the secreted form of the heavy chain (extracellular, intracellular and transmembrane segments are indicated) 

557 nucleotides 3 of the polyadenylation signal. This region might have been involved in the gene conversion event which is proposed to have taken place during evolution of the Ca genes [137], 

Another interesting sequence located upstream of mouse Cs as well as of mouse Cy3 consists of alternating purines. Coincidentally or not, (AG)28 is found 5 of both genes in Cy3 it is 389 nucleotides upstream of CH1 and in Cs it is 768 nucleotides upstream of an open reading frame between the membrane /x exons and Cgl [117,102]. However, functional significance of these sequence motifs has not been demonstrated. 

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LeuShik, FR,RHaue, KJ uan Berg, and A M van Leusen J Chain Soc, Chain Comniui., 1401 nVyl)... 

Figure 50-10. Schematic representation of serum igA, secretory igA, and igM. Both igA and igM have a J chain, but oniy secretory igA has a secretory component. Poiypeptide chains are represented by thick iines disuifide bonds iinking different poiypeptide chains are represented by thin iines. (Reproduced, with permission, from ParslowTG et al [editors] Medical Immunology, 10th ed. McGraw-Hill, 2001.)...

More recently, recombinant antibodies (mostly IgGs) have been produced in the milk of transgenic animals [21,22]. In particular, one study with transgenic mice has shown that it is possible to produce a porcine chimeric IgA that can form dimers in the presence of the J chain [23]. However, the production of fully assembled slgA has yet to be reported. 

The ability to stack genes in transgenic plants by successive crosses between individually transformed parental plants is a considerable advantage in attempting to construct multimeric protein complexes, such as secretory antibodies. As described earher, slgA consists of two basic Ig monomeric units (heavy and tight chains) that are dimerized by a joining (J) chain and then associated with a fourth polypeptide, the secretory component (SC) [36]. 

Figure 1.12. Schematic representation of an IgM molecule. Each IgM molecule comprises five IgG molecules joined by disulphide bonds and a J chain. Although the molecule has a predicted valency of 10 (i.e. a single IgM molecule can bind 10 molecules of antigen), this number is not reached in practice.

The 15-kDa J chain is synthesised by the same B-cell clone that produces the IgA molecule. The IgA molecules are transported across the epithelial cells and enter the lumen, this transport being mediated via another protein called the secretory chain (SC). The IgA molecules that are finally secreted are dimers of relative molecular mass of 400 kDa. The heavily glycosylated SC (80 kDa), synthesised and secreted by the epithelial cells, binds to the IgA molecules via non-covalent bonds. The IgA molecule thus has a valency of 4 (i.e. a single molecule has four antigen-binding sites), with all four sites recognising the same antigen. 

Figure 1.13. Schematic representation of an IgA molecule. Each IgA molecule comprises immunoglobulin molecules joined to each other via a J chain. The heavy chains possess three constant regions (Co1 Cce). The secretory chain (SC) is secreted by epithelial cells and binds to the IgA dimer via disulphide bonds (indicated by wriggly lines).

CR3 comprises two polypeptides, an a-subunit of 185 kDa and a -sub-unit of 95 kDa, which are covalently linked into an a fl structure. Both chains are exposed at the cell surface, whilst the a-chain forms the major portion of the ligand-binding site. The /J-subunit is common to the other adhesins, LFA-1 and pi50,95. These have an antigenically-distinct a-chain but a common /J-chain (see Fig. 3.6). Of these three receptors with common j3-chains, only CR3 binds significant amounts of C3bi. 

Other adhesion receptors that are structurally and functionally related include the receptors for fibronectin, vitronectin, platelet glycoproteins 13b and Ilia and the VLA (very-late antigen) series. All molecules involved in adhesion recognise the RGD motif and require the divalent cations Ca2+ and Mg2+ for binding. All are dimers of glycosylated proteins with relative molecular masses 95-190 kDa. There is also some sequence homology between the /J-chain (CD18) and one chain of the fibronectin receptor. 

IgA is associated mainly with seromucous secretions such as saliva, tears, nasal fluids, etc., and is secreted as a dimer with both a J chain and a secretor piece (relative molecular mass 70 000), the latter apparently to prevent damage to the molecule by proteolytic enzymes. Its major role appears to be the protection of mucous membranes and its presence in blood, mainly as the monomer, may be as a result of absorption of the degraded dimer. 

Cattaneo, A. and Neuberger, M.S., Polymeric immunoglobulin M is secreted by transfectants of non-lymphoid cells in the absence of immunoglobulin J chain, EMBO ]., 6, 2753-2758, 1987. 

Dimers and polymers of IgA are found in the various external secretions such as gastrointestinal, colostrum, seminal, and vaginal secretions, saliva, tears, nasal, bile, urine, and tracheobronchial secretions. Parotid saliva has an IgGrIgA ratio of about 0.01 compared to 4.5 for serum (T5). Four types of polypeptide chains have been identified in S IgA the light chain, MW 22,500 the hea y chain, MW 55,000 the secretory component (SC), MW 60,000 and the joining (J) chain, MW 20,000. 

The joining chain (J in Figs. 1 and 2) is attached to IgA in the submucosa, forming the 10 S dimer which, by the process of pinocytosis, enters the mucosa and there becomes attached to the secretory component (SC), giving rise to the 11 S dimer. Secretory component prevents hydrolysis of S IgA in the lumen of the gut. The 7 S IgA monomer does not become attached to the J chain but enters the circulation via the venous-lymphatic circulation. This physicochemical property of IgA probably accounts for its relatively increased values in the serum of some children with kwashiorkor. 

Figure 8.4 Model of a poly(dimethylsiloxane) [PDMS, (Me2SiO)J chain with a fourfold helical conformation, (a) Top view (b) side view (oxygen atoms are in black). Reproduced with permission from P.-A. Albouy, Polymer, 2000, 41, 3083. ...

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