User:Immcarle193/J chain
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[edit]Structure
[edit]The J Chain is a glycoprotein of molecular weight 15 kDa. Its secondary structure remains undetermined but is believed to adopt either a single β-barrel or two-domain folded structure.[1] The J chain's primary structure is unusually acidic having a high content of negatively charged amino acids.[2] It has 8 cysteine residues, 6 of which are involved in intramolecular disulfide bonds while the remaining two function to bind the Fc tailpiece regions of IgA or IgM antibodies. An N-linked carbohydrate resulting from N-glycosylation is also essential in the protein's incorporation to antibody polymers.[3] There is no known protein family with significant homology to the J chain.[4]
Function
[edit]Antibody Polymerization
[edit]The J chain regulates the multimerization of IgM and IgA in mammals. When expressed in cells, it favors the formation of a pentameric IgM and an IgA dimer.
The J chain is incorporated late in the formation of IgM polymers and thermodynamically favors the formation of pentamers as opposed to hexamers.[3] In J chain-KO mice, the hexameric IgM polymer dominates.[5] These J-chain negative IgM hexamers are 15-20 times more effective at activating complement than J-chain positive IgM pentamers.[6] However, J chain-KO mice have been shown have low concentrations of hexameric IgM and a deficiency in complement activation suggesting additional in vivo regulatory mechanisms.[7] IgM pentamers are most commonly found with a single J Chain, but some studies have seen as many as 4 stoichiometric equivalents.[8]
The J chain facilitates IgA dimerization by linking two monomer secretory tails. Structurally, the J chain joins two antibody monomers asymmetrically by forming intermolecular disulfide bonds and brining hydrophobic β-sandwiches on each molecule together.[9] This multimerization mechanism involves chaperone proteins including binding immunoglobulin protein (BiP) and MZB1 each sequentially recruiting distinct factors of the polymerized antibody.[10]
Antibody Secretion
[edit]Mucosal membrane antibody secretion from basal to apical epithelial cells is facilitated by the polymeric Ig receptor (pIgR). A basal protein of the pIgR known as secretory component (SC) recognizes Ig ready for secretion.[11] The binding between the secretory component and secretory Ig is facilitated by the antibody's J Chain which makes physical contact with the secretory component in order to change the transporter's conformation to an open state.[12] The complex is then transcytosed and the secretory component proteolytically cleaved from the receptor releasing the antibody in the apical side of the epithelial cell and to the lumen at large. This mechanism is thought to be largely conserved between the secretion of IgM and IgA.[10]
Regulation
[edit]J chain was originally believed to only be expressed in antibody-secreting plasma cells, however, the J chain has been seen to be expressed in earlier stages of B cell differentiation prior to Ig expression.[13] J chain expression is believed to occur in the early stages of lymphoid cell differentiation as it is expressed in both B and T cell precursors. As cells develop, it seems that expression of the μ-chain becomes necessary for J chain synthesis.[14]
The J chain gene is transcriptionally regulated through canonical Pax5 repression.[15] As Pax5 is a common transcriptional regulator, the J chain is still expressed in plasma cells that secrete monomeric antibodies. In such cells it is believed to provide no function and is quickly degraded.[10] In plasma cells that secrete monomeric IgA, a Pax5-independent mechanism is likely to prevent IgA dimerization.[16]
Phylogeny
[edit]The J Chain is likely to have evolutionarily arisen in early jaw-boned vertebrates.[17] Groups of bony fish including teleosts have since lost J Chain expression.[4] Xenopus are able to polymerize mucosal IgX in the absence of J Chain, perhaps due to a loss of the conserved cysteine residues that link the J Chain and Ig secretory tail.[18]
Sharks do not express IgA and thus use J Chain expression solely for the polymerization of IgM.[19] This makes sharks an intriguing model organism in studying J Chain regulation and polymerization without the confounding variables of mucosal secretion.[20]
References
[edit]- ^ Frutiger, Severine; Hughes, Graham; Paquet, Nicole; Luthy, Roland; Jaton, Jean-Claude. "Disulfide Bond Assignment in Human J Chain and Its Covalent Pairing with Immunoglobulin M". Biochemistry. 31: 12643–12647.
- ^ Klimovich, V. B.; Samoilovich, M. P.; Klimovich, B. V. (2008-04-01). "Problem of J-chain of immunoglobulins". Journal of Evolutionary Biochemistry and Physiology. 44 (2): 151–166. doi:10.1134/S0022093008020023. ISSN 1608-3202.
- ^ a b Sørensen, Vigdis; Rasmussen, Ingunn B.; Sundvold, Vibeke; Michaelsen, Terje E.; Sandlie, Inger (2000). "Structural requirements for incorporation of J chain into human IgM and IgA". International Immunology. 12 (1): 19. ISSN 1460-2377.
- ^ a b Castro, Caitlin D.; Flajnik, Martin F. (2014-10-01). "Putting J-chain back on the map: how might its expression define plasma cell development?". Journal of immunology (Baltimore, Md. : 1950). 193 (7): 3248–3255. doi:10.4049/jimmunol.1400531. ISSN 0022-1767. PMC 4198949. PMID 25240020.
- ^ Davis, A. C.; Roux, K. H.; Shulman, M. J. (1988-07). "On the structure of polymeric IgM". European Journal of Immunology. 18 (7): 1001–1008. doi:10.1002/eji.1830180705. ISSN 0014-2980. PMID 3136022.
{{cite journal}}: Check date values in:|date=(help) - ^ Johansen; Braathen; Brandtzaeg (2000-09). "Role of J Chain in Secretory Immunoglobulin Formation". Scandinavian Journal of Immunology. 52 (3): 240–248. doi:10.1046/j.1365-3083.2000.00790.x. ISSN 0300-9475.
{{cite journal}}: Check date values in:|date=(help) - ^ Erlandsson, L.; Andersson, K.; Sigvardsson, M.; Lycke, N.; Leanderson, T. (1998-08). "Mice with an inactivated joining chain locus have perturbed IgM secretion". European Journal of Immunology. 28 (8): 2355–2365. doi:10.1002/(SICI)1521-4141(199808)28:08<2355::AID-IMMU2355>3.0.CO;2-L. ISSN 0014-2980. PMID 9710213.
{{cite journal}}: Check date values in:|date=(help) - ^ Grubb, Anders O. (2009-04-24). "Quantitation of J Chain in Human Biological Fluids by a Simple Immunochemical Procedure". Acta Medica Scandinavica. 204 (1–6): 453–465. doi:10.1111/j.0954-6820.1978.tb08473.x.
- ^ Kumar, Nikit; Arthur, Christopher P.; Ciferri, Claudio; Matsumoto, Marissa L. (2020-02-28). "Structure of the secretory immunoglobulin A core". Science. 367 (6481): 1008–1014. doi:10.1126/science.aaz5807. ISSN 0036-8075.
- ^ a b c Wei, Hao; Wang, Ji-Yang (January, 2021). "Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis". International Journal of Molecular Sciences. 22 (5): 2284. doi:10.3390/ijms22052284. ISSN 1422-0067.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: unflagged free DOI (link) - ^ Stadtmueller, Beth M; Huey-Tubman, Kathryn E; López, Carlos J; Yang, Zhongyu; Hubbell, Wayne L; Bjorkman, Pamela J (2016-03-04). Kuriyan, John (ed.). "The structure and dynamics of secretory component and its interactions with polymeric immunoglobulins". eLife. 5: e10640. doi:10.7554/eLife.10640. ISSN 2050-084X.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Braathen, Ranveig; Hohman, Valerie S.; Brandtzaeg, Per; Johansen, Finn-Erik. "Secretory Antibody Formation: Conserved Binding Interactions between J Chain and Polymeric Ig Receptor from Humans and Amphibians". journals.aai.org. Retrieved 2023-02-02.
- ^ Mestecky, Jiri; Fultz, Patricia N. (1999). "Mucosal Immune System of the Human Genital Tract". The Journal of Infectious Diseases. 179: S470–S474. ISSN 0022-1899.
- ^ Max, E. E.; Korsmeyer, S. J. (1985-04-01). "Human J chain gene. Structure and expression in B lymphoid cells". The Journal of Experimental Medicine. 161 (4): 832–849. doi:10.1084/jem.161.4.832. ISSN 0022-1007. PMC 2189063. PMID 2984306.
- ^ Rao, S.; Karray, S.; Gackstetter, E. R.; Koshland, M. E. (1998-10-02). "Myocyte enhancer factor-related B-MEF2 is developmentally expressed in B cells and regulates the immunoglobulin J chain promoter". The Journal of Biological Chemistry. 273 (40): 26123–26129. doi:10.1074/jbc.273.40.26123. ISSN 0021-9258. PMID 9748293.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Hajdu, I.; Moldoveanu, Z.; Cooper, M. D.; Mestecky, J. (1983-12-01). "Ultrastructural studies of human lymphoid cells. mu and J chain expression as a function of B cell differentiation". The Journal of Experimental Medicine. 158 (6): 1993–2006. doi:10.1084/jem.158.6.1993. ISSN 0022-1007. PMC 2187181. PMID 6417260.
- ^ Marchalonis, J.; Edelman, G. M. (1965-09-01). "PHYLOGENETIC ORIGINS OF ANTIBODY STRUCTURE". The Journal of Experimental Medicine. 122 (3): 601–618. ISSN 0022-1007. PMC 2138074. PMID 4158437.
- ^ Robert, Jacques; Ohta, Yuko (2009-6). "Comparative and Developmental Study of the Immune System in Xenopus". Developmental dynamics : an official publication of the American Association of Anatomists. 238 (6): 1249–1270. doi:10.1002/dvdy.21891. ISSN 1058-8388. PMC 2892269. PMID 19253402.
{{cite journal}}: Check date values in:|date=(help) - ^ Clem, I. W.; De Boutaud, F.; Sigel, M. M. (1967-12). "Phylogeny of immunoglobulin structure and function. II. Immunoglobulins of the nurse shark". Journal of Immunology (Baltimore, Md.: 1950). 99 (6): 1226–1235. ISSN 0022-1767. PMID 4168665.
{{cite journal}}: Check date values in:|date=(help) - ^ Hohman, Valerie S.; Stewart, Sue E.; Rumfelt, Lynn L.; Greenberg, Andrew S.; Avila, David W.; Flajnik, Martin F.; Steiner, Lisa A. (2003-06-15). "J chain in the nurse shark: implications for function in a lower vertebrate". Journal of Immunology (Baltimore, Md.: 1950). 170 (12): 6016–6023. doi:10.4049/jimmunol.170.12.6016. ISSN 0022-1767. PMID 12794129.