[en] Lysine N-pyrrolation, a posttranslational modification, which converts lysine residues to N ε -pyrrole-L-lysine, imparts electronegative properties to proteins, causing them to mimic DNA. Apolipoprotein E (apoE) has been identified as a soluble receptor for pyrrolated proteins (pyrP), and accelerated lysine N-pyrrolation has been observed in apoE-deficient (apoE−/−) hyperlipidemic mice. However, the impact of pyrP accumulation consequent to apoE deficiency on the innate immune response remains unclear. Here, we investigated B-1a cells known to produce germline-encoded immunoglobulin M (IgM) from mice deficient in apoE and identified a particular cell population that specifically produces IgM antibodies against pyrP and DNA. We demonstrated an expansion of B-1a cells involved in IgM production in the peritoneal cavity of apoE−/− mice compared with wild-type mice, consistent with a progressive increase of IgM response in the mouse sera. We found that pyrP exhibited preferential binding to B-1a cells and facilitated the production of IgM. B cell receptor analysis of pyrP-specific B-1a cells showed restricted usage of gene segments selected from the germline gene set; most sequences contained high levels of non-templated-nucleotide additions (N-additions) that could contribute to junctional diversity of B cell receptors. Finally, we report that a subset of monoclonal IgM antibodies against pyrP/DNA established from the apoE−/− mice also contained abundant N-additions. These results suggest that the accumulation of pyrP due to apoE deficiency may influence clonal diversity in the pyrP-specific B cell repertoire. The discovery of these unique B-1a cells for pyrP/DNA provides a key link connecting covalent protein modification, lipoprotein metabolism, and innate immunity.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Lim, Sei-Young
Yamaguchi, Kosuke
ITAKURA, Masanori ; University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Neuroinflammation Group
Chikazawa, Miho
Matsuda, Tomonari
Uchida, Koji
External co-authors :
yes
Language :
English
Title :
Unique B-1 cells specific for both N-pyrrolated proteins and DNA evolve with apolipoprotein E deficiency
Publication date :
2022
Journal title :
Journal of Biological Chemistry
ISSN :
0021-9258
eISSN :
1083-351X
Publisher :
American Society for Biochemistry and Molecular Biology, Us md
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Bibliography
Stadtman, E. R., and Levine, R. L. (2000) Protein oxidation. Ann. N. Y. Acad. Sci. 899, 191-208
Stocker, R., and Keaney, J. F. (2004) Role of oxidative modifications in atherosclerosis. Physiol. Rev. 84, 1381-1478
Goldin, A., Beckman, J. A., Schmidt, A. M., and Creager, M. A. (2006) Advanced glycation end products: Sparking the development of diabetic vascular injury. Circulation 114, 597-605
Grimsrud, P. A., Xie, H., Griffin, T. J., and Bernlohr, D. A. (2008) Oxidative stress and covalent modification of protein with bioactive aldehydes. J. Biol. Chem. 283, 21837-21841
Grönwall, C., Vas, J., and Silverman, G. J. (2012) Protective roles of natural IgM antibodies. Front. Immunol. 3, 66
Chou, M.-Y., Fogelstrand, L., Hartvigsen, K., Hansen, L. F., Woelkers, D., Shaw, P. X., Choi, J., Perkmann, T., Bäckhed, F., Miller, Y. I., Hörkkö, S., Corr, M., Witztum, J. L., and Binder, C. J. (2009) Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans. J. Clin. Invest. 119, 1335-1349
Boes, M., Prodeus, A. P., Schmidt, T., Carroll, M. C., and Chen, J. (1998) A critical role of natural immunoglobulin M in immediate defense against systemic bacterial infection. J. Exp. Med. 188, 2381-2386
Baumgarth, N., Herman, O. C., Jager, G. C., Brown, L. E., Herzenberg, L. A., and Chen, J. (2000) B-1 and B-2 cell-derived immunoglobulin M antibodies are nonredundant components of the protective response to influenza virus infection. J. Exp. Med. 192, 271-280
Haas, K. M., Poe, J. C., Steeber, D. A., and Tedder, T. F. (2005) B-1a and B-1b cells exhibit distinct developmental requirements and have unique functional roles in innate and adaptive immunity to S. pneumoniae. Immunity 23, 7-18
Mercolino, T. J., Arnold, L. W., Hawkins, L. A., and Haughton, G. (1988) Normal mouse peritoneum contains a large population of Ly-1+ (CD5) B cells that recognize phosphatidyl choline. Relationship to cells that secrete hemolytic antibody specific for autologous erythrocytes. J. Exp. Med. 168, 687-698
Chikazawa, M., Otaki, N., Shibata, T., Miyashita, H., Kawai, Y., Maruyama, S., Toyokuni, S., Kitaura, Y., Matsuda, T., and Uchida, K. (2013) Multispecificity of immunoglobulin M antibodies raised against advanced glycation end products: Involvement of electronegative potential of antigens. J. Biol. Chem. 288, 13204-13214
Bello-Gil, D., Khasbiullina, N., Shilova, N., Bovin, N., and Mañez, R. (2017) Repertoire of BALB/c mice natural anti-carbohydrate antibodies: Mice vs. humans difference, and otherness of individual animals. Front. Immunol. 8, 1449
Endo, R., Uchiyama, K., Lim, S.-Y., Itakura, M., Adachi, T., and Uchida, K. (2021) Recognition of acrolein-specific epitopes by B cell receptors triggers an innate immune response. J. Biol. Chem. 296, 100648
Miyashita, H., Chikazawa, M., Otaki, N., Hioki, Y., Shimozu, Y., Nakashima, F., Shibata, T., Hagihara, Y., Maruyama, S., Matsumi, N., and Uchida, K. (2014) Lysine pyrrolation is a naturally-occurring covalent modification involved in the production of DNA mimic proteins. Sci. Rep. 4, 5343
Hirose, S., Hioki, Y., Miyashita, H., Hirade, N., Yoshitake, J., Shibata, T., Kikuchi, R., Matsushita, T., Chikazawa, M., Itakura, M., Zhang, M., Nagata, K., and Uchida, K. (2019) Apolipoprotein E binds to and reduces serum levels of DNA-mimicking, pyrrolated proteins. J. Biol. Chem. 294, 11035-11045
Xu, J. L., and Davis, M. M. (2000) Diversity in the CDR3 region of V(H) is sufficient for most antibody specificities. Immunity 13, 37-45
Tonegawa, S. (1983) Somatic generation of antibody diversity. Nature 302, 575-581
Gu, H., Förster, I., and Rajewsky, K. (1990) Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: Implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B-CLL progenitor generation. EMBO J. 9, 2133-2140
Feeney, A. J. (1992) Comparison of junctional diversity in the neonatal and adult immunoglobulin repertoires. Int. Rev. Immunol. 8, 113-122
Krishnan, M. R., Jou, N. T., and Marion, T. N. (1996) Correlation between the amino acid position of arginine in VH-CDR3 and specificity for native DNA among autoimmune antibodies. J. Immunol. 157, 2430-2439
Chikazawa, M., Yoshitake, J., Lim, S.-Y., Iwata, S., Negishi, L., Shibata, T., and Uchida, K. (2020) Glycolaldehyde is an endogenous source of lysine N-pyrrolation. J. Biol. Chem. 295, 7697-7709
Sayre, L. M., Arora, P. K., and Salomon, R. G. (1993) Pyrrole formation from 4-hydroxynonenal and primary amines. Chem. Res. Toxicol. 6, 19-22
Itakura, K., Osawa, T., and Uchida, K. (1998) Structure of a fluorescent compound formed from 4-hydroxy-2-nonenal and Nϵ-hippuryllysine: A model for fluorophores derived from protein modifications by lipid peroxidation. J. Org. Chem. 63, 185-187
Hidalgo, F. J., and Zamora, R. (1993) Fluorescent pyrrole products from carbonyl-amine reactions. J. Biol. Chem. 268, 16190-16197
Zhang, W.-H., Liu, J., Xu, G., Yuan, Q., and Sayre, L. M. (2003) Model studies on protein side chain modification by 4-oxo-2-nonenal. Chem. Res. Toxicol. 16, 512-523
Salomon, R. G., Subbanagounder, G., O'Neil, J., Smith, M. A., Hoff, H. F., Perry, G., and Monnier, V. M. (1997) Levuglandin E2-protein adducts in human plasma and vasculature. Chem. Res. Toxicol. 10, 536-545
Hidalgo, F. J., and Zamora, R. (1995) Epoxyoxoene fatty esters: Key intermediates for the synthesis of long chain pyrrole and furan fatty esters. Chem. Phys. Lipids 77, 1-11
Zhou, Y., Cheshire, A., Howell, L. A., Ryan, D. H., and Harris, R. B. (1999) Neuroautoantibody immunoreactivity in relation to aging and stress in apolipoprotein E-deficient mice. Brain Res. Bull. 49, 173-179
Ma, Z., Choudhury, A., Kang, S.-A., Monestier, M., Cohen, P. L., and Eisenberg, R. A. (2008) Accelerated atherosclerosis in ApoE deficient lupus mouse models. Clin. Immunol. 127, 168-175
Hutchinson, M. A., Park, H.-S., Zanotti, K. J., Alvarez-Gonzalez, J., Zhang, J., Zhang, L., Telljohann, R., Wang, M., Lakatta, E. G., Gearhart, P. J., and Maul, R. W. (2021) Auto-antibody production during experimental atherosclerosis in ApoE-/- Mice. Front. Immunol. 12, 695220
Wang, Y., Huang, Z., Lu, H., Lin, H., Wang, Z., Chen, X., Ouyang, Q., Tang, M., Hao, P., Ni, J., Xu, D., Zhang, M., Zhang, Q., Lin, L., and Zhang, Y. (2012) Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies. Biochem. Biophys. Res. Commun. 423, 805-812
Ansar Ahmed, S., Dauphinée, M. J., Montoya, A. I., and Talal, N. (1989) Estrogen induces normal murine CD5+ B cells to produce autoantibodies. J. Immunol. 142, 2647-2653
Hayakawa, K., Hardy, R. R., Parks, D. R., and Herzenberg, L. A. (1983) The "Ly-1 B" cell subpopulation in normal immunodefective, and autoimmune mice. J. Exp. Med. 157, 202-218
Berland, R., and Wortis, H. H. (2002) Origins and functions of B-1 cells with notes on the role of CD5. Annu. Rev. Immunol. 20, 253-300
Hayakawa, K., Asano, M., Shinton, S. A., Gui, M., Allman, D., Stewart, C. L., Silver, J., and Hardy, R. R. (1999) Positive selection of natural autoreactive B cells. Science 285, 113-116
Yang, Y., Wang, C., Yang, Q., Kantor, A. B., Chu, H., Ghosn, E. E., Qin, G., Mazmanian, S. K., Han, J., and Herzenberg, L. A. (2015) Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires. Elife 4, e09083
Prohaska, T. A., Que, X., Diehl, C. J., Hendrikx, S., Chang, M. W., Jepsen, K., Glass, C. K., Benner, C., and Witztum, J. L. (2018) Massively parallel sequencing of peritoneal and splenic B cell repertoires highlights unique properties of B-1 cell antibodies. J. Immunol. 200, 1702-1717
Tsuji, N., Rothstein, T. L., and Holodick, N. E. (2020) Antigen receptor specificity and cell location influence the diversification and selection of the B-1a cell pool with age. J. Immunol. 205, 741-759
Hayakawa, K., Hardy, R. R., Stall, A. M., Herzenberg, L. A., and Herzenberg, L. A. (1986) Immunoglobulin-bearing B cells reconstitute and maintain the murine Ly-1 B cell lineage. Eur. J. Immunol. 16, 1313-1316
Kantor, A. B. (1996) V-gene usage and N-region insertions in B-1a, B-1b and conventional B cells. Semin. Immunol. 8, 29-35
Huang, C. A., Henry, C., Iacomini, J., Imanishi-Kari, T., and Wortis, H. H. (1996) Adult bone marrow contains precursors for CD5+ B cells. Eur. J. Immunol. 26, 2537-2540
Holodick, N. E., Vizconde, T., and Rothstein, T. L. (2014) B-1a cell diversity: Nontemplated addition in B-1a cell Ig is determined by progenitor population and developmental location. J. Immunol. 192, 2432-2441
Wloch, M. K., Alexander, A. L., Pippen, A. M., Pisetsky, D. S., and Gilkeson, G. S. (1996) Differences in V kappa gene utilization and VH CDR3 sequence among anti-DNA from C3H-lpr mice and lupus mice with nephritis. Eur. J. Immunol. 26, 2225-2233
Krishnan, M. R., and Marion, T. N. (1998) Comparison of the frequencies of arginines in heavy chain CDR3 of antibodies expressed in the primary B-cell repertoires of autoimmune-prone and normal mice. Scand. J. Immunol. 48, 223-232
Jethwa, H. S., Clarke, S. H., Itoh-Lindstrom, Y., Falk, R. J., Jennette, J. C., and Nachman, P. H. (2000) Restriction in V kappa gene use and antigen selection in anti-myeloperoxidase response in mice. J. Immunol. 165, 3890-3897
Eilat, D., Webster, D. M., and Rees, A. R. (1988) V region sequences of anti-DNA and anti-RNA autoantibodies from NZB/NZW F1 mice. J. Immunol. 141, 1745-1753
Ibrahim, S. M., Weigert, M., Basu, C., Erikson, J., and Radic, M. Z. (1995) Light chain contribution to specificity in anti-DNA antibodies. J. Immunol. 155, 3223-3233
Wloch, M. K., Alexander, A. L., Pippen, A. M., Pisetsky, D. S., and Gilkeson, G. S. (1997) Molecular properties of anti-DNA induced in preautoimmune NZB/W mice by immunization with bacterial DNA. J. Immunol. 158, 4500-4506
Zemlin, M., Klinger, M., Link, J., Zemlin, C., Bauer, K., Engler, J. A., Schroeder, H. W., and Kirkham, P. M. (2003) Expressed murine and human CDR-H3 intervals of equal length exhibit distinct repertoires that differ in their amino acid composition and predicted range of structures. J. Mol. Biol. 334, 733-749
Mian, I. S., Bradwell, A. R., and Olson, A. J. (1991) Structure, function and properties of antibody binding sites. J. Mol. Biol. 217, 133-151
Fellouse, F. A., Wiesmann, C., and Sidhu, S. S. (2004) Synthetic antibodies from a four-amino-acid code: A dominant role for tyrosine in antigen recognition. Proc. Natl. Acad. Sci. U. S. A. 101, 12467-12472
Fellouse, F. A., Li, B., Compaan, D. M., Peden, A. A., Hymowitz, S. G., and Sidhu, S. S. (2005) Molecular recognition by a binary code. J. Mol. Biol. 348, 1153-1162
Lam, K. P., Kühn, R., and Rajewsky, K. (1997) In vivo ablation of surface immunoglobulin on mature B cells by inducible gene targeting results in rapid cell death. Cell 90, 1073-1083
Rees, M. S., van Kuijk, F. J. G. M., Stephens, R. J., and Mundy, B. P. (1993) Synthesis of deuterated 4-hydroxyalkenals. Synth. Commun. 23, 757-763
Rindgen, D., Nakajima, M., Wehrli, S., Xu, K., and Blair, I. A. (1999) Covalent modifications to 2'-deoxyguanosine by 4-oxo-2-nonenal, a novel product of lipid peroxidation. Chem. Res. Toxicol. 12, 1195-1204
Fröhlich, J., Lehmkuhl, K., Fröhlich, R., and Wünsch, B. (2015) Diastereoselective synthesis of cyclic five-membered trans, trans-configured nitrodiols by double Henry reaction of 1, 4-dialdehydes. Arch. Pharm. 348, 589-594
Marnett, L. J., and Tuttle, M. A. (1980) Comparison of the mutagenicities of malondialdehyde and the side products formed during its chemical synthesis. Cancer Res. 40, 276-282
Genestier, L., Taillardet, M., Mondiere, P., Gheit, H., Bella, C., and Defrance, T. (2007) TLR agonists selectively promote terminal plasma cell differentiation of B cell subsets specialized in thymus-independent responses. J. Immunol. 178, 7779-7786
Lefranc, M.-P., Giudicelli, V., Kaas, Q., Duprat, E., Jabado-Michaloud, J., Scaviner, D., Ginestoux, C., Clément, O., Chaume, D., and Lefranc, G. (2005) IMGT, the international ImMunoGeneTics information system. Nucleic Acids Res. 33, D593-D597
Crooks, G. E., Hon, G., Chandonia, J.-M., and Brenner, S. E. (2004) WebLogo: A sequence logo generator. Genome Res. 14, 1188-1190
Tiller, T., Busse, C. E., and Wardemann, H. (2009) Cloning and expression of murine Ig genes from single B cells. J. Immunol. Methods 350, 183-193
Hara, Y., Dong, J., and Ueda, H. (2013) Open-sandwich immunoassay for sensitive and broad-range detection of a shellfish toxin gonyautoxin. Anal. Chim. Acta 793, 107-113
Ye, J., Ma, N., Madden, T. L., and Ostell, J. M. (2013) IgBLAST: An immunoglobulin variable domain sequence analysis tool. Nucleic Acids Res. 41, W34-W40
