CD1d Selectively Down Regulates the Expression of the Oxidized Phospholipid-Specific E06 IgM Natural Antibody in <i>Ldlr<sup>−/−</sup></i> Mice
Natural antibodies (NAbs) are important regulators of tissue homeostasis and inflammation and are thought to have diverse protective roles in a variety of pathological states. E06 is a T15 idiotype IgM NAb exclusively produced by B-1 cells, which recognizes the phosphocholine (PC) head group in oxid...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Antibodies |
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| Online Access: | https://www.mdpi.com/2073-4468/9/3/30 |
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| author | Tapan K. Biswas Paul A. VanderLaan Xuchu Que Ayelet Gonen Paulette Krishack Christoph J. Binder Joseph L. Witztum Godfrey S. Getz Catherine A. Reardon |
| author_facet | Tapan K. Biswas Paul A. VanderLaan Xuchu Que Ayelet Gonen Paulette Krishack Christoph J. Binder Joseph L. Witztum Godfrey S. Getz Catherine A. Reardon |
| author_sort | Tapan K. Biswas |
| collection | DOAJ |
| description | Natural antibodies (NAbs) are important regulators of tissue homeostasis and inflammation and are thought to have diverse protective roles in a variety of pathological states. E06 is a T15 idiotype IgM NAb exclusively produced by B-1 cells, which recognizes the phosphocholine (PC) head group in oxidized phospholipids on the surface of apoptotic cells and in oxidized LDL (OxLDL), and the PC present on the cell wall of <i>Streptococcus pneumoniae</i>. Here we report that titers of the E06 NAb are selectively increased several-fold in <i>Cd1d</i>-deficient mice, whereas total IgM and IgM antibodies recognizing other oxidation specific epitopes such as in malondialdehyde-modified LDL (MDA-LDL) and OxLDL were not increased. The high titers of E06 in <i>Cd1d</i>-deficient mice are not due to a global increase in IgM-secreting B-1 cells, but they are specifically due to an expansion of E06-secreting splenic B-1 cells. Thus, CD1d-mediated regulation appeared to be suppressive in nature and specific for E06 IgM-secreting cells. The CD1d-mediated regulation of the E06 NAb generation is a novel mechanism that regulates the production of this specific oxidation epitope recognizing NAb. |
| first_indexed | 2024-03-10T18:42:43Z |
| format | Article |
| id | doaj.art-a63e5d9ba0bf4b0a9b3c18adfd39be96 |
| institution | Directory Open Access Journal |
| issn | 2073-4468 |
| language | English |
| last_indexed | 2024-03-10T18:42:43Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibodies |
| spelling | doaj.art-a63e5d9ba0bf4b0a9b3c18adfd39be962023-11-20T05:44:01ZengMDPI AGAntibodies2073-44682020-07-01933010.3390/antib9030030CD1d Selectively Down Regulates the Expression of the Oxidized Phospholipid-Specific E06 IgM Natural Antibody in <i>Ldlr<sup>−/−</sup></i> MiceTapan K. Biswas0Paul A. VanderLaan1Xuchu Que2Ayelet Gonen3Paulette Krishack4Christoph J. Binder5Joseph L. Witztum6Godfrey S. Getz7Catherine A. Reardon8Department of Pathology, University of Chicago, Chicago, IL 60637, USADepartment of Pathology, University of Chicago, Chicago, IL 60637, USADepartment of Medicine, University of California, San Diego, La Jolla, CA 92093, USADepartment of Medicine, University of California, San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of Chicago, Chicago, IL 60637, USADepartment of Laboratory Medicine, Medical University of Vienna, Vienna 1090, AustriaDepartment of Medicine, University of California, San Diego, La Jolla, CA 92093, USADepartment of Pathology, University of Chicago, Chicago, IL 60637, USADepartment of Pathology, University of Chicago, Chicago, IL 60637, USANatural antibodies (NAbs) are important regulators of tissue homeostasis and inflammation and are thought to have diverse protective roles in a variety of pathological states. E06 is a T15 idiotype IgM NAb exclusively produced by B-1 cells, which recognizes the phosphocholine (PC) head group in oxidized phospholipids on the surface of apoptotic cells and in oxidized LDL (OxLDL), and the PC present on the cell wall of <i>Streptococcus pneumoniae</i>. Here we report that titers of the E06 NAb are selectively increased several-fold in <i>Cd1d</i>-deficient mice, whereas total IgM and IgM antibodies recognizing other oxidation specific epitopes such as in malondialdehyde-modified LDL (MDA-LDL) and OxLDL were not increased. The high titers of E06 in <i>Cd1d</i>-deficient mice are not due to a global increase in IgM-secreting B-1 cells, but they are specifically due to an expansion of E06-secreting splenic B-1 cells. Thus, CD1d-mediated regulation appeared to be suppressive in nature and specific for E06 IgM-secreting cells. The CD1d-mediated regulation of the E06 NAb generation is a novel mechanism that regulates the production of this specific oxidation epitope recognizing NAb.https://www.mdpi.com/2073-4468/9/3/30natural antibodiesCD1doxidized lipidsinnate immunity |
| spellingShingle | Tapan K. Biswas Paul A. VanderLaan Xuchu Que Ayelet Gonen Paulette Krishack Christoph J. Binder Joseph L. Witztum Godfrey S. Getz Catherine A. Reardon CD1d Selectively Down Regulates the Expression of the Oxidized Phospholipid-Specific E06 IgM Natural Antibody in <i>Ldlr<sup>−/−</sup></i> Mice Antibodies natural antibodies CD1d oxidized lipids innate immunity |
| title | CD1d Selectively Down Regulates the Expression of the Oxidized Phospholipid-Specific E06 IgM Natural Antibody in <i>Ldlr<sup>−/−</sup></i> Mice |
| title_full | CD1d Selectively Down Regulates the Expression of the Oxidized Phospholipid-Specific E06 IgM Natural Antibody in <i>Ldlr<sup>−/−</sup></i> Mice |
| title_fullStr | CD1d Selectively Down Regulates the Expression of the Oxidized Phospholipid-Specific E06 IgM Natural Antibody in <i>Ldlr<sup>−/−</sup></i> Mice |
| title_full_unstemmed | CD1d Selectively Down Regulates the Expression of the Oxidized Phospholipid-Specific E06 IgM Natural Antibody in <i>Ldlr<sup>−/−</sup></i> Mice |
| title_short | CD1d Selectively Down Regulates the Expression of the Oxidized Phospholipid-Specific E06 IgM Natural Antibody in <i>Ldlr<sup>−/−</sup></i> Mice |
| title_sort | cd1d selectively down regulates the expression of the oxidized phospholipid specific e06 igm natural antibody in i ldlr sup sup i mice |
| topic | natural antibodies CD1d oxidized lipids innate immunity |
| url | https://www.mdpi.com/2073-4468/9/3/30 |
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