Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunity
Abstract B cells engage in anti-tumor immunity but how they contribute to cancer suppression remains unclear. We report that inhibiting plasma cell differentiation either in IgMi mice lacking Igh elements needed for antibody secretion or in mice with B cell-specific knockout of Blimp-1 (Blimp-1 BcKO...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59622-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850273523257311232 |
|---|---|
| author | Yunqiao Li Raag Bhargava Jenny Tuyet Tran Tanya R. Blane Linghang Peng Fangkun Luan Zhe Huang Zefan Zhang Yunfan Sun Changchun Xiao David Nemazee |
| author_facet | Yunqiao Li Raag Bhargava Jenny Tuyet Tran Tanya R. Blane Linghang Peng Fangkun Luan Zhe Huang Zefan Zhang Yunfan Sun Changchun Xiao David Nemazee |
| author_sort | Yunqiao Li |
| collection | DOAJ |
| description | Abstract B cells engage in anti-tumor immunity but how they contribute to cancer suppression remains unclear. We report that inhibiting plasma cell differentiation either in IgMi mice lacking Igh elements needed for antibody secretion or in mice with B cell-specific knockout of Blimp-1 (Blimp-1 BcKO) promotes rather than inhibits antitumor immunity and increases numbers of activated B cells. Deficiency of Blimp-1 in tumor-infiltrating B cells generates a unique transcription profile associated with expansion of mutated clones targeting cognate tumor cells. Major histocompatibility complex class II (MHC II) is required for anti-tumor efficacy. Blimp-1-deficient B cells have increased expression of CD80 and CD86 costimulatory molecules that enhance effector T cell function. The Blimp-1 inhibitor valproic acid suppresses tumor growth in a B cell-dependent manner. Thus, inhibition of plasma cell differentiation results in enhanced tumor-specific antigen presentation by B cells and thereby tumor repression, suggesting a potential avenue of immunotherapy against cancer. |
| format | Article |
| id | doaj-art-9d78a995441d4fa483566fef318807e8 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9d78a995441d4fa483566fef318807e82025-08-20T01:51:28ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-59622-4Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunityYunqiao Li0Raag Bhargava1Jenny Tuyet Tran2Tanya R. Blane3Linghang Peng4Fangkun Luan5Zhe Huang6Zefan Zhang7Yunfan Sun8Changchun Xiao9David Nemazee10Department of Immunology and Microbiology, The Scripps Research InstituteDepartment of Immunology and Microbiology, The Scripps Research InstituteDepartment of Immunology and Microbiology, The Scripps Research InstituteDepartment of Immunology and Microbiology, The Scripps Research InstituteDepartment of Immunology and Microbiology, The Scripps Research InstituteDepartment of Immunology and Microbiology, The Scripps Research InstituteDepartment of Immunology and Microbiology, The Scripps Research InstituteDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of EducationDepartment of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of EducationDepartment of Immunology and Microbiology, The Scripps Research InstituteDepartment of Immunology and Microbiology, The Scripps Research InstituteAbstract B cells engage in anti-tumor immunity but how they contribute to cancer suppression remains unclear. We report that inhibiting plasma cell differentiation either in IgMi mice lacking Igh elements needed for antibody secretion or in mice with B cell-specific knockout of Blimp-1 (Blimp-1 BcKO) promotes rather than inhibits antitumor immunity and increases numbers of activated B cells. Deficiency of Blimp-1 in tumor-infiltrating B cells generates a unique transcription profile associated with expansion of mutated clones targeting cognate tumor cells. Major histocompatibility complex class II (MHC II) is required for anti-tumor efficacy. Blimp-1-deficient B cells have increased expression of CD80 and CD86 costimulatory molecules that enhance effector T cell function. The Blimp-1 inhibitor valproic acid suppresses tumor growth in a B cell-dependent manner. Thus, inhibition of plasma cell differentiation results in enhanced tumor-specific antigen presentation by B cells and thereby tumor repression, suggesting a potential avenue of immunotherapy against cancer.https://doi.org/10.1038/s41467-025-59622-4 |
| spellingShingle | Yunqiao Li Raag Bhargava Jenny Tuyet Tran Tanya R. Blane Linghang Peng Fangkun Luan Zhe Huang Zefan Zhang Yunfan Sun Changchun Xiao David Nemazee Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunity Nature Communications |
| title | Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunity |
| title_full | Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunity |
| title_fullStr | Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunity |
| title_full_unstemmed | Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunity |
| title_short | Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunity |
| title_sort | blocking plasma cell fate enhances antigen specific presentation by b cells to boost anti tumor immunity |
| url | https://doi.org/10.1038/s41467-025-59622-4 |
| work_keys_str_mv | AT yunqiaoli blockingplasmacellfateenhancesantigenspecificpresentationbybcellstoboostantitumorimmunity AT raagbhargava blockingplasmacellfateenhancesantigenspecificpresentationbybcellstoboostantitumorimmunity AT jennytuyettran blockingplasmacellfateenhancesantigenspecificpresentationbybcellstoboostantitumorimmunity AT tanyarblane blockingplasmacellfateenhancesantigenspecificpresentationbybcellstoboostantitumorimmunity AT linghangpeng blockingplasmacellfateenhancesantigenspecificpresentationbybcellstoboostantitumorimmunity AT fangkunluan blockingplasmacellfateenhancesantigenspecificpresentationbybcellstoboostantitumorimmunity AT zhehuang blockingplasmacellfateenhancesantigenspecificpresentationbybcellstoboostantitumorimmunity AT zefanzhang blockingplasmacellfateenhancesantigenspecificpresentationbybcellstoboostantitumorimmunity AT yunfansun blockingplasmacellfateenhancesantigenspecificpresentationbybcellstoboostantitumorimmunity AT changchunxiao blockingplasmacellfateenhancesantigenspecificpresentationbybcellstoboostantitumorimmunity AT davidnemazee blockingplasmacellfateenhancesantigenspecificpresentationbybcellstoboostantitumorimmunity |