The Clonal Diversity of Peripheral B Cell Receptor Immune Repertoire Impaired by Residual Malignant B Cells Predicts Treatment Efficacy in B Cell Lymphoma Patients
Germinal center (GC) is the vital locus for the evolution of naïve B cells into memory B and plasma cells, but also a hotbed for the proliferation of malignant B cells. We hypothesized that malignant B cells may locally or globally impact GCs to produce peripheral B cell receptor immune repertoire (...
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MDPI AG
2022-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/19/4628 |
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| author | Meng Wu Jing Zhang Yi Wang Lan Mi Xiaopei Wang Weiping Liu Jie Fu Haifeng Song Yuqin Song Jun Zhu |
| author_facet | Meng Wu Jing Zhang Yi Wang Lan Mi Xiaopei Wang Weiping Liu Jie Fu Haifeng Song Yuqin Song Jun Zhu |
| author_sort | Meng Wu |
| collection | DOAJ |
| description | Germinal center (GC) is the vital locus for the evolution of naïve B cells into memory B and plasma cells, but also a hotbed for the proliferation of malignant B cells. We hypothesized that malignant B cells may locally or globally impact GCs to produce peripheral B cell receptor immune repertoire (BCR IR) with reduced clonal diversity. In this study, we first validated our hypothesis in a novel human in-vitro GC (hiGC) model. The addition of the diffuse large B cell lymphoma (DLBCL) cells to the hiGC culture attenuated the rate of diversity growth. For clinical validation, we collected samples from 17 DLBCL patients at various points during high-dose therapy and autologous stem cell rescue. The elimination and reestablishment of the patients’ lymphatic pool allowed us to unambiguously monitor the impact of tumor cells on the replenishment of the peripheral BCR IR. Compared to the nine patients who did not relapse after treatment, relapsed patients tended to have a slower rate of recovery regarding the clonal diversity of their peripheral BCR IR. Our results suggest a mechanistic and clinical connection between residual tumor cells and abnormal peripheral BCR IR, which may corelate with treatment efficacy in B cell lymphomas. |
| first_indexed | 2024-03-09T21:59:11Z |
| format | Article |
| id | doaj.art-fd29c5cf56924385a5423b91cbb7ea3f |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T21:59:11Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-fd29c5cf56924385a5423b91cbb7ea3f2023-11-23T19:53:56ZengMDPI AGCancers2072-66942022-09-011419462810.3390/cancers14194628The Clonal Diversity of Peripheral B Cell Receptor Immune Repertoire Impaired by Residual Malignant B Cells Predicts Treatment Efficacy in B Cell Lymphoma PatientsMeng Wu0Jing Zhang1Yi Wang2Lan Mi3Xiaopei Wang4Weiping Liu5Jie Fu6Haifeng Song7Yuqin Song8Jun Zhu9Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaState Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaGerminal center (GC) is the vital locus for the evolution of naïve B cells into memory B and plasma cells, but also a hotbed for the proliferation of malignant B cells. We hypothesized that malignant B cells may locally or globally impact GCs to produce peripheral B cell receptor immune repertoire (BCR IR) with reduced clonal diversity. In this study, we first validated our hypothesis in a novel human in-vitro GC (hiGC) model. The addition of the diffuse large B cell lymphoma (DLBCL) cells to the hiGC culture attenuated the rate of diversity growth. For clinical validation, we collected samples from 17 DLBCL patients at various points during high-dose therapy and autologous stem cell rescue. The elimination and reestablishment of the patients’ lymphatic pool allowed us to unambiguously monitor the impact of tumor cells on the replenishment of the peripheral BCR IR. Compared to the nine patients who did not relapse after treatment, relapsed patients tended to have a slower rate of recovery regarding the clonal diversity of their peripheral BCR IR. Our results suggest a mechanistic and clinical connection between residual tumor cells and abnormal peripheral BCR IR, which may corelate with treatment efficacy in B cell lymphomas.https://www.mdpi.com/2072-6694/14/19/4628germinal centerB cell receptor immune repertoireB cell lymphomaclonal diversitysomatic hypermutation |
| spellingShingle | Meng Wu Jing Zhang Yi Wang Lan Mi Xiaopei Wang Weiping Liu Jie Fu Haifeng Song Yuqin Song Jun Zhu The Clonal Diversity of Peripheral B Cell Receptor Immune Repertoire Impaired by Residual Malignant B Cells Predicts Treatment Efficacy in B Cell Lymphoma Patients Cancers germinal center B cell receptor immune repertoire B cell lymphoma clonal diversity somatic hypermutation |
| title | The Clonal Diversity of Peripheral B Cell Receptor Immune Repertoire Impaired by Residual Malignant B Cells Predicts Treatment Efficacy in B Cell Lymphoma Patients |
| title_full | The Clonal Diversity of Peripheral B Cell Receptor Immune Repertoire Impaired by Residual Malignant B Cells Predicts Treatment Efficacy in B Cell Lymphoma Patients |
| title_fullStr | The Clonal Diversity of Peripheral B Cell Receptor Immune Repertoire Impaired by Residual Malignant B Cells Predicts Treatment Efficacy in B Cell Lymphoma Patients |
| title_full_unstemmed | The Clonal Diversity of Peripheral B Cell Receptor Immune Repertoire Impaired by Residual Malignant B Cells Predicts Treatment Efficacy in B Cell Lymphoma Patients |
| title_short | The Clonal Diversity of Peripheral B Cell Receptor Immune Repertoire Impaired by Residual Malignant B Cells Predicts Treatment Efficacy in B Cell Lymphoma Patients |
| title_sort | clonal diversity of peripheral b cell receptor immune repertoire impaired by residual malignant b cells predicts treatment efficacy in b cell lymphoma patients |
| topic | germinal center B cell receptor immune repertoire B cell lymphoma clonal diversity somatic hypermutation |
| url | https://www.mdpi.com/2072-6694/14/19/4628 |
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