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CD4+ T cell dependent B cell recovery and function after autologous hematopoietic stem cell transplantation

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Item Type:Article
Title:CD4+ T cell dependent B cell recovery and function after autologous hematopoietic stem cell transplantation
Creators Name:Heck, C. and Steiner, S. and Kaebisch, E.M. and Frentsch, M. and Wittenbecher, F. and Scheibenbogen, C. and Hanitsch, L.G. and Nogai, A. and le Coutre, P. and Bullinger, L. and Blau, I.W. and Na, I.K.
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.
Keywords:B Cell Defects, Autologous Hematopoiectic Stem Cell Transplantation, T Cell Dependent B Cell Activation, Immune Reconstitution, Multiple Myeloma, Secondary Immunodeficiencies
Source:Frontiers in Immunology
ISSN:1664-3224
Publisher:Frontiers Media SA
Volume:12
Page Range:736137
Date:September 2021
Official Publication:https://doi.org/10.3389/fimmu.2021.736137
PubMed:View item in PubMed

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