The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal Centers
To understand how the Bcl6 transcriptional repressor functions in the immune system, we disrupted its RD2 repression domain in mice. Bcl6RD2MUT mice exhibit a complete loss of germinal center (GC) formation but retain normal extrafollicular responses. Bcl6RD2MUT antigen-engaged B cells migrate to th...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-09-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124714006627 |
| _version_ | 1818143145685155840 |
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| author | Chuanxin Huang David G. Gonzalez Christine M. Cote Yanwen Jiang Katerina Hatzi Matt Teater Kezhi Dai Timothy Hla Ann M. Haberman Ari Melnick |
| author_facet | Chuanxin Huang David G. Gonzalez Christine M. Cote Yanwen Jiang Katerina Hatzi Matt Teater Kezhi Dai Timothy Hla Ann M. Haberman Ari Melnick |
| author_sort | Chuanxin Huang |
| collection | DOAJ |
| description | To understand how the Bcl6 transcriptional repressor functions in the immune system, we disrupted its RD2 repression domain in mice. Bcl6RD2MUT mice exhibit a complete loss of germinal center (GC) formation but retain normal extrafollicular responses. Bcl6RD2MUT antigen-engaged B cells migrate to the interfollicular zone and interact with cognate T helper cells. However, these cells fail to complete early GC-commitment differentiation and coalesce as nascent GC aggregates. Bcl6 directly binds and represses trafficking receptors S1pr1 and Gpr183 by recruiting Hdac2 through the RD2 domain. Deregulation of these genes impairs B cell migration and may contribute to GC failure in Bcl6RD2MUT mice. The development of functional GC-TFH cells was partially impaired in Bcl6RD2MUT mice. In contrast to Bcl6−/− mice, Bcl6RD2MUT animals experience no inflammatory disease or macrophage deregulation. These results reveal an essential role for RD2 repression in early GC commitment and striking biochemical specificity in Bcl6 control of humoral and innate immune-cell phenotypes. |
| first_indexed | 2024-12-11T11:27:01Z |
| format | Article |
| id | doaj.art-1ed162acc18c444ea8b0a2f5b7b9e0c9 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T11:27:01Z |
| publishDate | 2014-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-1ed162acc18c444ea8b0a2f5b7b9e0c92022-12-22T01:08:59ZengElsevierCell Reports2211-12472014-09-01851497150810.1016/j.celrep.2014.07.059The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal CentersChuanxin Huang0David G. Gonzalez1Christine M. Cote2Yanwen Jiang3Katerina Hatzi4Matt Teater5Kezhi Dai6Timothy Hla7Ann M. Haberman8Ari Melnick9Division of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USADepartment of Laboratory Medicine and Immunobiology, Yale University, New Haven, CT 06520, USADepartment of Laboratory Medicine and Immunobiology, Yale University, New Haven, CT 06520, USADivision of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USADivision of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USADivision of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USADepartment of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065, USADepartment of Laboratory Medicine and Immunobiology, Yale University, New Haven, CT 06520, USADivision of Hematology and Oncology, Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USATo understand how the Bcl6 transcriptional repressor functions in the immune system, we disrupted its RD2 repression domain in mice. Bcl6RD2MUT mice exhibit a complete loss of germinal center (GC) formation but retain normal extrafollicular responses. Bcl6RD2MUT antigen-engaged B cells migrate to the interfollicular zone and interact with cognate T helper cells. However, these cells fail to complete early GC-commitment differentiation and coalesce as nascent GC aggregates. Bcl6 directly binds and represses trafficking receptors S1pr1 and Gpr183 by recruiting Hdac2 through the RD2 domain. Deregulation of these genes impairs B cell migration and may contribute to GC failure in Bcl6RD2MUT mice. The development of functional GC-TFH cells was partially impaired in Bcl6RD2MUT mice. In contrast to Bcl6−/− mice, Bcl6RD2MUT animals experience no inflammatory disease or macrophage deregulation. These results reveal an essential role for RD2 repression in early GC commitment and striking biochemical specificity in Bcl6 control of humoral and innate immune-cell phenotypes.http://www.sciencedirect.com/science/article/pii/S2211124714006627 |
| spellingShingle | Chuanxin Huang David G. Gonzalez Christine M. Cote Yanwen Jiang Katerina Hatzi Matt Teater Kezhi Dai Timothy Hla Ann M. Haberman Ari Melnick The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal Centers Cell Reports |
| title | The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal Centers |
| title_full | The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal Centers |
| title_fullStr | The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal Centers |
| title_full_unstemmed | The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal Centers |
| title_short | The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal Centers |
| title_sort | bcl6 rd2 domain governs commitment of activated b cells to form germinal centers |
| url | http://www.sciencedirect.com/science/article/pii/S2211124714006627 |
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