Key Points Amplification of 1q21 correlates with increased sensitivity to MCL-1 inhibitor S63845 in primary MM cells. Poor-prognosis MM is particularly sensitive to MCL-1 inhibition, partially independent of 1q21 amplification status.

Mucosal lymphoid tissues such as human tonsil are colonized by bacteria and exposed to ingested and inhaled antigens, requiring tight regulation of immune responses. Antibody responses are regulated by follicular helper T (TFH) cells and FOXP3+ follicular regulatory T (TFR) cells. Here we describe a subset of human tonsillar follicular T cells identified by expression of TFH markers and CD25 that are the main source of follicular T (TF) cell–derived IL-10. Despite lack of FOXP3 expression, CD25+ TF cells resemble T reg cells in high CTLA4 expression, low IL-2 production, and their ability to repress T cell proliferation. CD25+ TF cell–derived IL-10 dampens induction of B cell class-switching to IgE. In children, circulating total IgE titers were inversely correlated with the frequencies of tonsil CD25+ TF cells and IL-10–producing TF cells but not with total T reg cells, TFR, or IL-10–producing T cells. Thus, CD25+ TF cells emerge as a subset with unique T and B cell regulatory activities that may help prevent atopy.

CD molecules are surface molecules expressed on cells of the immune system that play key roles in immune cell-cell communication and sensing the microenvironment. These molecules are essential markers for the identification and isolation of leukocytes and lymphocyte subsets. Here, we present the results of the first phase of the CD Maps study, mapping the expression of CD1–CD100 (n = 110) on 47 immune cell subsets from blood, thymus, and tonsil using an eight-color standardized EuroFlow approach and quantification of expression. The resulting dataset included median antibody binding capacities (ABCs) and percentage of positivity for all markers on all subsets and was developed into an interactive CD Maps web resource. Using the resource, we examined differentially expressed proteins between granulocyte, monocyte, and dendritic cell subsets, and profiled dynamic expression of markers during thymocyte differentiation, T-cell maturation, and between functionally distinct B-cell subset clusters. The CD Maps resource will serve as a benchmark of antibody reactivities ensuring improved reproducibility of flow cytometry-based research. Moreover, it will provide a full picture of the surfaceome of human immune cells and serves as a useful platform to increase our understanding of leukocyte biology, as well as to facilitate the identification of new biomarkers and therapeutic targets of immunological and hematological diseases.

Signaling lymphocytic activation molecule family (SLAMF) receptors and the specific adapter SLAM-associated protein (SAP) modulate the development of innate-like lymphocytes. Here, we show that the thymus of Ly9-deficient mice contains an expanded population of CD8 single-positive cells with the characteristic phenotype of innate memory-like CD8+ T-cells. Moreover, the proportion of these innate CD8+ T-cells increased dramatically after infection with mouse cytomegalovirus. Gene expression profiling of Ly9-deficient mice thymi showed a significant up-regulation of IL-4 and PLZF. Analyses of Ly9−/−IL4ra−/− double-deficient mice revealed that IL-4 was needed to generate the thymic innate CD8+ T-cell subset. Furthermore, increased numbers of iNKT cells were detected in Ly9-deficient thymi. In wild-type mice IL-4 levels induced by αGalCer injection could be inhibited by a monoclonal antibody against Ly9. Thus, Ly9 plays a unique role as an inhibitory cell-surface receptor regulating the size of the thymic innate CD8+ T-cell pool and the development of iNKT cells.