CD4+ T Cell Dependent B Cell Recovery and Function After Autologous Hematopoietic Stem Cell Transplantation

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

Evaluation of Phosphite and Phosphane Stabilized Copper(I) Trifluoroacetates as Precursors for the Metal-Organic Chemical Vapor Deposition of Copper

Copper has become the material of choice for metallization of high-performance ultra-large scale integrated circuits. As the feature size is continuously decreasing, metal-organic chemical vapor deposition (MOCVD) appears promising for depositing the Cu seed layer required for electroplating, as well as for filling entire interconnect structures. In this work, four novel organophosphane and organophosphite Cu(I) trifluoroacetates were studied as precursors for Cu MOCVD. Details are reported on CVD results obtained with Tris(tri-n-butylphosphane)copper(I)trifluoroacetate, (nBu3P)3CuO2CCF3. Solutions of this precursor with acetonitrile and isopropanol were used for deposition experiments on 100 mm Si wafers sputter-coated with Cu, Cu/TiN, and Al(2 % Si)/W. Experiments were carried out in a cold-wall reactor at a pressure of 0.7 mbar, using a liquid delivery approach for precursor dosage. On Cu seed layers, continuous films were obtained at low deposition rates (0.5 to 1 nm/min). At temperatures above 320°C, hole formation in the Cu films was observed. Deposition on TiN led to the formation of single copper particles and etching of the TiN, whereas isolating aluminum oxyfluoride was formed after deposition on Al(Si)/W. It is concluded that the formation of CF3 radicals during decarboxylation has a negative effect on the deposition results. Furthermore, the precursor chemistry needs to be improved for a higher volatility of the complex