T-bet+CD27+CD21– B cells poised for plasma cell differentiation during antibody-mediated rejection of kidney transplants
Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Kevin Louis [verfasserIn] Elodie Bailly [verfasserIn] Camila Macedo [verfasserIn] Louis Lau [verfasserIn] Bala Ramaswami [verfasserIn] Alexander Chang [verfasserIn] Uma Chandran [verfasserIn] Douglas Landsittel [verfasserIn] Xinyan Gu [verfasserIn] Geetha Chalasani [verfasserIn] Adriana Zeevi [verfasserIn] Parmjeet Randhawa [verfasserIn] Harinder Singh [verfasserIn] Carmen Lefaucheur [verfasserIn] Diana Metes [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: JCI Insight - American Society for Clinical investigation, 2020, 6(2021), 12 |
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| Übergeordnetes Werk: |
volume:6 ; year:2021 ; number:12 |
| Links: |
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DOAJ043315623 |
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| 520 | |a Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets. | ||
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(DE-627)DOAJ043315623 (DE-599)DOAJ6e3a7b3fbce24424adc7139960536e1c DE-627 ger DE-627 rakwb eng Kevin Louis verfasserin aut T-bet+CD27+CD21– B cells poised for plasma cell differentiation during antibody-mediated rejection of kidney transplants 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets. Immunology Transplantation Medicine R Elodie Bailly verfasserin aut Camila Macedo verfasserin aut Louis Lau verfasserin aut Bala Ramaswami verfasserin aut Alexander Chang verfasserin aut Uma Chandran verfasserin aut Douglas Landsittel verfasserin aut Xinyan Gu verfasserin aut Geetha Chalasani verfasserin aut Adriana Zeevi verfasserin aut Parmjeet Randhawa verfasserin aut Harinder Singh verfasserin aut Carmen Lefaucheur verfasserin aut Diana Metes verfasserin aut In JCI Insight American Society for Clinical investigation, 2020 6(2021), 12 (DE-627)872610594 (DE-600)2874757-4 23793708 nnns volume:6 year:2021 number:12 https://doaj.org/article/6e3a7b3fbce24424adc7139960536e1c kostenfrei https://doi.org/10.1172/jci.insight.148881 kostenfrei https://doaj.org/toc/2379-3708 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2021 12 |
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(DE-627)DOAJ043315623 (DE-599)DOAJ6e3a7b3fbce24424adc7139960536e1c DE-627 ger DE-627 rakwb eng Kevin Louis verfasserin aut T-bet+CD27+CD21– B cells poised for plasma cell differentiation during antibody-mediated rejection of kidney transplants 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets. Immunology Transplantation Medicine R Elodie Bailly verfasserin aut Camila Macedo verfasserin aut Louis Lau verfasserin aut Bala Ramaswami verfasserin aut Alexander Chang verfasserin aut Uma Chandran verfasserin aut Douglas Landsittel verfasserin aut Xinyan Gu verfasserin aut Geetha Chalasani verfasserin aut Adriana Zeevi verfasserin aut Parmjeet Randhawa verfasserin aut Harinder Singh verfasserin aut Carmen Lefaucheur verfasserin aut Diana Metes verfasserin aut In JCI Insight American Society for Clinical investigation, 2020 6(2021), 12 (DE-627)872610594 (DE-600)2874757-4 23793708 nnns volume:6 year:2021 number:12 https://doaj.org/article/6e3a7b3fbce24424adc7139960536e1c kostenfrei https://doi.org/10.1172/jci.insight.148881 kostenfrei https://doaj.org/toc/2379-3708 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2021 12 |
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(DE-627)DOAJ043315623 (DE-599)DOAJ6e3a7b3fbce24424adc7139960536e1c DE-627 ger DE-627 rakwb eng Kevin Louis verfasserin aut T-bet+CD27+CD21– B cells poised for plasma cell differentiation during antibody-mediated rejection of kidney transplants 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets. Immunology Transplantation Medicine R Elodie Bailly verfasserin aut Camila Macedo verfasserin aut Louis Lau verfasserin aut Bala Ramaswami verfasserin aut Alexander Chang verfasserin aut Uma Chandran verfasserin aut Douglas Landsittel verfasserin aut Xinyan Gu verfasserin aut Geetha Chalasani verfasserin aut Adriana Zeevi verfasserin aut Parmjeet Randhawa verfasserin aut Harinder Singh verfasserin aut Carmen Lefaucheur verfasserin aut Diana Metes verfasserin aut In JCI Insight American Society for Clinical investigation, 2020 6(2021), 12 (DE-627)872610594 (DE-600)2874757-4 23793708 nnns volume:6 year:2021 number:12 https://doaj.org/article/6e3a7b3fbce24424adc7139960536e1c kostenfrei https://doi.org/10.1172/jci.insight.148881 kostenfrei https://doaj.org/toc/2379-3708 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2021 12 |
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(DE-627)DOAJ043315623 (DE-599)DOAJ6e3a7b3fbce24424adc7139960536e1c DE-627 ger DE-627 rakwb eng Kevin Louis verfasserin aut T-bet+CD27+CD21– B cells poised for plasma cell differentiation during antibody-mediated rejection of kidney transplants 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets. Immunology Transplantation Medicine R Elodie Bailly verfasserin aut Camila Macedo verfasserin aut Louis Lau verfasserin aut Bala Ramaswami verfasserin aut Alexander Chang verfasserin aut Uma Chandran verfasserin aut Douglas Landsittel verfasserin aut Xinyan Gu verfasserin aut Geetha Chalasani verfasserin aut Adriana Zeevi verfasserin aut Parmjeet Randhawa verfasserin aut Harinder Singh verfasserin aut Carmen Lefaucheur verfasserin aut Diana Metes verfasserin aut In JCI Insight American Society for Clinical investigation, 2020 6(2021), 12 (DE-627)872610594 (DE-600)2874757-4 23793708 nnns volume:6 year:2021 number:12 https://doaj.org/article/6e3a7b3fbce24424adc7139960536e1c kostenfrei https://doi.org/10.1172/jci.insight.148881 kostenfrei https://doaj.org/toc/2379-3708 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2021 12 |
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(DE-627)DOAJ043315623 (DE-599)DOAJ6e3a7b3fbce24424adc7139960536e1c DE-627 ger DE-627 rakwb eng Kevin Louis verfasserin aut T-bet+CD27+CD21– B cells poised for plasma cell differentiation during antibody-mediated rejection of kidney transplants 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets. Immunology Transplantation Medicine R Elodie Bailly verfasserin aut Camila Macedo verfasserin aut Louis Lau verfasserin aut Bala Ramaswami verfasserin aut Alexander Chang verfasserin aut Uma Chandran verfasserin aut Douglas Landsittel verfasserin aut Xinyan Gu verfasserin aut Geetha Chalasani verfasserin aut Adriana Zeevi verfasserin aut Parmjeet Randhawa verfasserin aut Harinder Singh verfasserin aut Carmen Lefaucheur verfasserin aut Diana Metes verfasserin aut In JCI Insight American Society for Clinical investigation, 2020 6(2021), 12 (DE-627)872610594 (DE-600)2874757-4 23793708 nnns volume:6 year:2021 number:12 https://doaj.org/article/6e3a7b3fbce24424adc7139960536e1c kostenfrei https://doi.org/10.1172/jci.insight.148881 kostenfrei https://doaj.org/toc/2379-3708 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2021 12 |
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T-bet+CD27+CD21– B cells poised for plasma cell differentiation during antibody-mediated rejection of kidney transplants |
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Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets. |
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Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets. |
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Alloimmune responses driven by donor-specific antibodies (DSAs) can lead to antibody-mediated rejection (ABMR) in organ transplantation. Yet, the cellular states underlying alloreactive B cell responses and the molecular components controlling them remain unclear. Using high-dimensional profiling of B cells in a cohort of 96 kidney transplant recipients, we identified expanded numbers of CD27+CD21– activated memory (AM) B cells that expressed the transcription factor T-bet in patients who developed DSAs and progressed to ABMR. Notably, AM cells were less frequent in DSA+ABMR– patients and at baseline levels in DSA– patients. RNA-Seq analysis of AM cells in patients undergoing ABMR revealed these cells to be poised for plasma cell differentiation and to express restricted IGHV sequences reflective of clonal expansion. In addition to T-bet, AM cells manifested elevated expression of interferon regulatory factor 4 and Blimp1, and upon coculture with autologous T follicular helper cells, differentiated into DSA-producing plasma cells in an IL-21–dependent manner. The frequency of AM cells was correlated with the timing and severity of ABMR manifestations. Importantly, T-bet+ AM cells were detected within kidney allografts along with their restricted IGHV sequences. This study delineates a pivotal role for AM cells in promoting humoral responses and ABMR in organ transplantation and highlights them as important therapeutic targets. |
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