dc.contributor.author
Heck, Clarissa
dc.contributor.author
Steiner, Sophie
dc.contributor.author
Kaebisch, Eva M.
dc.contributor.author
Frentsch, Marco
dc.contributor.author
Wittenbecher, Friedrich
dc.contributor.author
Scheibenbogen, Carmen
dc.contributor.author
Hanitsch, Leif G.
dc.contributor.author
Nogai, Axel
dc.contributor.author
le Coutre, Philipp
dc.contributor.author
Bullinger, Lars
dc.contributor.author
Blau, Igor-Wolfgang
dc.contributor.author
Na, Il-Kang
dc.date.accessioned
2022-01-20T10:10:14Z
dc.date.available
2022-01-20T10:10:14Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/33644
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-33364
dc.description.abstract
Introduction: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) represents a standard treatment regime for multiple myeloma (MM) patients. Common and potentially fatal side effects after auto-HSCT are infections due to a severely compromised immune system with hampered humoral and cellular immunity. This study delineates in depth the quantitative and functional B cell defects and investigates underlying extrinsic or intrinsic drivers.
Methods: Peripheral blood of MM patients undergoing high-dose chemotherapy and auto-HSCT (before high-dose chemotherapy and in early reconstitution after HSCT) was studied. Absolute numbers and distribution of B cell subsets were analyzed ex vivo using flow cytometry. Additionally, B cell function was assessed with T cell dependent (TD) and T cell independent (TI) stimulation assays, analyzing proliferation and differentiation of B cells by flow cytometry and numbers of immunoglobulin secreting cells in ELISpots.
Results: Quantitative B cell defects including a shift in the B cell subset distribution occurred after auto-HSCT. Functionally, these patients showed an impaired TD as well as TI B cell immune response. Individual functional responses correlated with quantitative alterations of CD19+, CD4+, memory B cells and marginal zone-like B cells. The TD B cell function could be partially restored upon stimulation with CD40L/IL-21, successfully inducing B cell proliferation and differentiation into plasmablasts and immunoglobulin secreting cells.
Conclusion: Quantitative and functional B cell defects contribute to the compromised immune defense in MM patients undergoing auto-HSCT. Functional recovery upon TD stimulation and correlation with CD4+ T cell numbers, indicate these as extrinsic drivers of the functional B cell defect. Observed correlations of CD4+, CD19+, memory B and MZ-like B cell numbers with the B cell function suggest that these markers should be tested as potential biomarkers in prospective studies.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
B cell defects
en
dc.subject
autologous hematopoiectic stem cell transplantation
en
dc.subject
T cell dependent B cell activation
en
dc.subject
immune reconstitution
en
dc.subject
multiple myeloma
en
dc.subject
secondary immunodeficiencies
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
CD4+ T Cell Dependent B Cell Recovery and Function After Autologous Hematopoietic Stem Cell Transplantation
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
736137
dcterms.bibliographicCitation.doi
10.3389/fimmu.2021.736137
dcterms.bibliographicCitation.journaltitle
Frontiers in Immunology
dcterms.bibliographicCitation.originalpublishername
Frontiers Media SA
dcterms.bibliographicCitation.volume
12
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
34659226
dcterms.isPartOf.eissn
1664-3224