Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is characterized by the overproduction of high-affinity autoreactive antibodies. Here, we show that more than 65.8% of 222 recombinant antibodies derived from 8 SLE patients can be secreted as heavy chain-only antibodies (HCAbs) when expressed in HEK-293T cells. Th...
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| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00632/full |
| _version_ | 1819098807026057216 |
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| author | Shu Xu Hong Yang Yue Zhuo Yangsheng Yu Hongyan Liao Song Li Yinshi Yue Kaihong Su Zhixin Zhang |
| author_facet | Shu Xu Hong Yang Yue Zhuo Yangsheng Yu Hongyan Liao Song Li Yinshi Yue Kaihong Su Zhixin Zhang |
| author_sort | Shu Xu |
| collection | DOAJ |
| description | Systemic lupus erythematosus (SLE) is characterized by the overproduction of high-affinity autoreactive antibodies. Here, we show that more than 65.8% of 222 recombinant antibodies derived from 8 SLE patients can be secreted as heavy chain-only antibodies (HCAbs) when expressed in HEK-293T cells. The secretion of HCAbs follows the conventional endoplasmic reticulum-Golgi apparatus pathway, despite triggering a weaker unfolded protein response (UPR). Many of the purified SLE HCAbs remain autoreactive and have an even higher affinity for dsDNA, Sm, nucleosome, and cardiolipin than HCAbs from healthy individuals. Extended analyses of the CDR3 region and the heavy chain variable (VH) region of HCAb F3 show that the VH region is responsible for IgH secretion, while the CDR3 region determines its reactivity. Such a high frequency of HCAb secretion cannot fully concur with our current understanding of antibody assembly and secretion. The presence of a large proportion of autoreactive HCAbs in SLE reveals a novel mechanism for the generation of autoreactive antibodies in lupus. |
| first_indexed | 2024-12-22T00:36:51Z |
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| id | doaj.art-cbb2bf789bfb45a4bf80d35be7a2a3a5 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T00:36:51Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-cbb2bf789bfb45a4bf80d35be7a2a3a52022-12-21T18:44:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00632449680Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus ErythematosusShu Xu0Hong Yang1Yue Zhuo2Yangsheng Yu3Hongyan Liao4Song Li5Yinshi Yue6Kaihong Su7Zhixin Zhang8State Key Laboratory of Biotherapy, Sichuan University, Chengdu, ChinaState Key Laboratory of Biotherapy, Sichuan University, Chengdu, ChinaHealth Management Center, Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United StatesDepartment of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Medical Oncology, Cancer Center, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United StatesEducation-Microbiology/Immunology, Department of Medical Education, California University of Science and Medicine, San Bernardino, CA, United StatesHealth Management Center, Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, ChinaSystemic lupus erythematosus (SLE) is characterized by the overproduction of high-affinity autoreactive antibodies. Here, we show that more than 65.8% of 222 recombinant antibodies derived from 8 SLE patients can be secreted as heavy chain-only antibodies (HCAbs) when expressed in HEK-293T cells. The secretion of HCAbs follows the conventional endoplasmic reticulum-Golgi apparatus pathway, despite triggering a weaker unfolded protein response (UPR). Many of the purified SLE HCAbs remain autoreactive and have an even higher affinity for dsDNA, Sm, nucleosome, and cardiolipin than HCAbs from healthy individuals. Extended analyses of the CDR3 region and the heavy chain variable (VH) region of HCAb F3 show that the VH region is responsible for IgH secretion, while the CDR3 region determines its reactivity. Such a high frequency of HCAb secretion cannot fully concur with our current understanding of antibody assembly and secretion. The presence of a large proportion of autoreactive HCAbs in SLE reveals a novel mechanism for the generation of autoreactive antibodies in lupus.https://www.frontiersin.org/article/10.3389/fimmu.2020.00632/fullB cellplasmablastheavy chain antibodypolyreactive antibodyautoreactive antibodysomatic hypermutation |
| spellingShingle | Shu Xu Hong Yang Yue Zhuo Yangsheng Yu Hongyan Liao Song Li Yinshi Yue Kaihong Su Zhixin Zhang Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus Erythematosus Frontiers in Immunology B cell plasmablast heavy chain antibody polyreactive antibody autoreactive antibody somatic hypermutation |
| title | Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus Erythematosus |
| title_full | Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus Erythematosus |
| title_fullStr | Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus Erythematosus |
| title_full_unstemmed | Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus Erythematosus |
| title_short | Production of Autoreactive Heavy Chain-Only Antibodies in Systemic Lupus Erythematosus |
| title_sort | production of autoreactive heavy chain only antibodies in systemic lupus erythematosus |
| topic | B cell plasmablast heavy chain antibody polyreactive antibody autoreactive antibody somatic hypermutation |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00632/full |
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