The immunoglobulin J chain is an evolutionarily co-opted chemokine.
| Autor: | Kawasaki K; Department of Anthropology, Pennsylvania State University, University Park, PA 16802., Ohta Y; Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201., Castro CD; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637., Flajnik MF; Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201. |
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| Jazyk: | angličtina |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jan 16; Vol. 121 (3), pp. e2318995121. Date of Electronic Publication: 2024 Jan 12. |
| DOI: | 10.1073/pnas.2318995121 |
| Abstrakt: | The joining (J) chain regulates polymerization of multimeric Immunoglobulin(Ig)M and IgA, forming a disulfide bond to the C termini of their Ig heavy chains, and it controls IgM/IgA transport across mucosal epithelia. Like Ig itself and human-like adaptive immunity, J chain emerged in jawed vertebrates (gnathostomes), but its origin has remained mysterious since its discovery over 50 y ago. Here, we show unexpectedly that J chain is a member of the CXCL chemokine family. The J chain gene ( JCHAIN ) is linked to clustered CXCL chemokine loci in all gnathostomes except actinopterygians that lost JCHAIN . JCHAIN and most CXCL genes have four exons with the same intron phases, including the same cleavage site for the signal peptide/mature protein. The second exon of both genes encodes a CXC motif at the same position, and the lengths of exons 1 to 3 are similar. No other gene in the human secretome shares all of these characteristics. In contrast, intrachain disulfide bonds of the two proteins are completely different, likely due to modifications in J chain to direct Ig polymerization and mucosal transport. Crystal structures of CXCL8 and J chain share a conserved beta-strand core but diverge otherwise due to different intrachain disulfide bonds and extension of the J chain C terminus. Identification of this ancestral affiliation between J chain and CXCL chemokines addresses an age-old problem in immunology. Competing Interests: Competing interests statement:The authors declare no competing interest. |
| Databáze: | MEDLINE |
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