Deficits in the IgG+ memory B‐cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques
Abstract Objectives Loss of vaccine‐induced antibodies (Abs) after chemotherapy against paediatric acute lymphoblastic leukaemia (ALL) is common and often necessitates re‐immunisation after cessation of treatment. Even so, some ALL survivors fail to mount or to maintain protective Abs. Germinal cent...
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doaj-fd96d3bb85f244d9a7931ad6aeed11732020-11-25T03:27:58ZengWileyClinical & Translational Immunology2050-00682020-01-0197n/an/a10.1002/cti2.1150Deficits in the IgG+ memory B‐cell recovery after anthracycline treatment is confined to the spleen of rhesus macaquesGintare Lasaviciute0Andréas L Bricaud1Fredrika Hellgren2Hanna M Ingelman‐Sundberg3Staffan Eksborg4Margreet Jonker5Krista G Haanstra6Ida Hed Myrberg7Eva Sverremark‐Ekström8Karin Loré9Shanie Saghafian‐Hedengren10Anna Nilsson11Departmet of Molecular Biosciences The Wenner‐Gren Institute Stockholm University Stockholm SwedenChildhood Cancer Research Unit Department of Women's and Children's Health Karolinska Institutet Stockholm SwedenDepartment of Medicine Solna Division of Immunology and Allergy Karolinska Institutet and Karolinska University Hospital Stockholm SwedenChildhood Cancer Research Unit Department of Women's and Children's Health Karolinska Institutet Stockholm SwedenChildhood Cancer Research Unit Department of Women's and Children's Health Karolinska Institutet Stockholm SwedenBiomedical Primate Research Centre (BPRC) Rijswijk The NetherlandsBiomedical Primate Research Centre (BPRC) Rijswijk The NetherlandsChildhood Cancer Research Unit Department of Women's and Children's Health Karolinska Institutet Stockholm SwedenDepartmet of Molecular Biosciences The Wenner‐Gren Institute Stockholm University Stockholm SwedenDepartment of Medicine Solna Division of Immunology and Allergy Karolinska Institutet and Karolinska University Hospital Stockholm SwedenDepartmet of Molecular Biosciences The Wenner‐Gren Institute Stockholm University Stockholm SwedenChildhood Cancer Research Unit Department of Women's and Children's Health Karolinska Institutet Stockholm SwedenAbstract Objectives Loss of vaccine‐induced antibodies (Abs) after chemotherapy against paediatric acute lymphoblastic leukaemia (ALL) is common and often necessitates re‐immunisation after cessation of treatment. Even so, some ALL survivors fail to mount or to maintain protective Abs. Germinal centres (GCs) are clusters of proliferating B cells in follicles of secondary lymphoid tissues (SLTs) formed during adaptive immune responses and the origins of long‐lived memory B and plasma cells that are the source of Abs. Furthermore, productive GC reactions depend on T follicular helper (TFH) cells. To understand why chemotherapy induces deficits in Ab responses, we examined how SLTs were affected by chemotherapy. Methods Rhesus macaques were infused with either three cycles of the anthracycline doxorubicin or saline, followed by immunisation with a de novo and booster antigen. Spleen and lymph nodes were removed, and memory B, bulk T and TFH cells were examined. Results Despite adequate GC morphology, a diminished memory and IgG+ B‐cell population along with diminished total and booster vaccine‐specific IgG‐producing memory B cells were noted in the spleens of macaques with past doxorubicin exposure compared to the saline‐treated controls (P < 0.05). Intact bulk T and TFH cells were found in the SLTs of treated macaques, which displayed higher CD40L upregulation capacity by their splenic CXCR5+ helper T cells (P < 0.01). In contrast to the spleen, the immune cell populations studied were comparable between the lymph nodes of both saline‐ and doxorubicin‐treated macaques. Conclusion Our findings suggest that the splenic memory B‐cell subset, compared to its lymph node counterpart, is more severely altered by anthracycline treatment.https://doi.org/10.1002/cti2.1150anthracyclinede novo and booster vaccinememory B‐cell responserhesus macaquesecondary lymphoid organs |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gintare Lasaviciute Andréas L Bricaud Fredrika Hellgren Hanna M Ingelman‐Sundberg Staffan Eksborg Margreet Jonker Krista G Haanstra Ida Hed Myrberg Eva Sverremark‐Ekström Karin Loré Shanie Saghafian‐Hedengren Anna Nilsson |
spellingShingle |
Gintare Lasaviciute Andréas L Bricaud Fredrika Hellgren Hanna M Ingelman‐Sundberg Staffan Eksborg Margreet Jonker Krista G Haanstra Ida Hed Myrberg Eva Sverremark‐Ekström Karin Loré Shanie Saghafian‐Hedengren Anna Nilsson Deficits in the IgG+ memory B‐cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques Clinical & Translational Immunology anthracycline de novo and booster vaccine memory B‐cell response rhesus macaque secondary lymphoid organs |
author_facet |
Gintare Lasaviciute Andréas L Bricaud Fredrika Hellgren Hanna M Ingelman‐Sundberg Staffan Eksborg Margreet Jonker Krista G Haanstra Ida Hed Myrberg Eva Sverremark‐Ekström Karin Loré Shanie Saghafian‐Hedengren Anna Nilsson |
author_sort |
Gintare Lasaviciute |
title |
Deficits in the IgG+ memory B‐cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques |
title_short |
Deficits in the IgG+ memory B‐cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques |
title_full |
Deficits in the IgG+ memory B‐cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques |
title_fullStr |
Deficits in the IgG+ memory B‐cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques |
title_full_unstemmed |
Deficits in the IgG+ memory B‐cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques |
title_sort |
deficits in the igg+ memory b‐cell recovery after anthracycline treatment is confined to the spleen of rhesus macaques |
publisher |
Wiley |
series |
Clinical & Translational Immunology |
issn |
2050-0068 |
publishDate |
2020-01-01 |
description |
Abstract Objectives Loss of vaccine‐induced antibodies (Abs) after chemotherapy against paediatric acute lymphoblastic leukaemia (ALL) is common and often necessitates re‐immunisation after cessation of treatment. Even so, some ALL survivors fail to mount or to maintain protective Abs. Germinal centres (GCs) are clusters of proliferating B cells in follicles of secondary lymphoid tissues (SLTs) formed during adaptive immune responses and the origins of long‐lived memory B and plasma cells that are the source of Abs. Furthermore, productive GC reactions depend on T follicular helper (TFH) cells. To understand why chemotherapy induces deficits in Ab responses, we examined how SLTs were affected by chemotherapy. Methods Rhesus macaques were infused with either three cycles of the anthracycline doxorubicin or saline, followed by immunisation with a de novo and booster antigen. Spleen and lymph nodes were removed, and memory B, bulk T and TFH cells were examined. Results Despite adequate GC morphology, a diminished memory and IgG+ B‐cell population along with diminished total and booster vaccine‐specific IgG‐producing memory B cells were noted in the spleens of macaques with past doxorubicin exposure compared to the saline‐treated controls (P < 0.05). Intact bulk T and TFH cells were found in the SLTs of treated macaques, which displayed higher CD40L upregulation capacity by their splenic CXCR5+ helper T cells (P < 0.01). In contrast to the spleen, the immune cell populations studied were comparable between the lymph nodes of both saline‐ and doxorubicin‐treated macaques. Conclusion Our findings suggest that the splenic memory B‐cell subset, compared to its lymph node counterpart, is more severely altered by anthracycline treatment. |
topic |
anthracycline de novo and booster vaccine memory B‐cell response rhesus macaque secondary lymphoid organs |
url |
https://doi.org/10.1002/cti2.1150 |
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