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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., Steiner, S., Kaebisch, E.M., Frentsch, M., Wittenbecher, F., Scheibenbogen, C., Hanitsch, L.G., Nogai, A., le Coutre, P., Bullinger, L., 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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