B cell immunoglobulin production is regulated by helper T cells through direct interaction and secreted cytokines. In the present study, we functionally analyzed CD27 in cord and peripheral blood B cells. Adult peripheral blood B cells were separated into CD27+ and CD27- cells, which differed in their morphology. Cord blood B cells did not express CD27, and CD27 expression on peripheral blood B cells increased with age. Only CD27+ B cells had the ability to produce immunoglobulin, which was increased by contact with a tumor necrosis factor-related transmembrane ligand, CD70. Adult peripheral blood CD27+ B cells can be further subdivided into two discrete subtypes: IgD- CD27+ and IgD+ CD27+ B cells. IgD- CD27+ B cells produce IgG, IgM and IgA, whereas IgD+ CD27+ B cells predominantly produce IgM. The addition of activated CD4+ CD45RO T cells expressing CD70 caused down-regulation of CD27 expression on activated B cells, and this down-modulation was completely blocked by anti-CD70 monoclonal antibody, indicating direct T-B cell contact via CD27/CD70. The triggering via CD27 and CD40 additively increased the immunoglobulin production under Staphylococcus aureus Cowan strain plus interleukin-2 stimulation. Taken together, our findings demonstrate that peripheral blood B cells are separated into subpopulations by CD27 and IgD expression and that CD27+ B cells produce large amounts of immunoglobulin by interaction with the CD70 molecule.

Nematomorph parasites manipulate crickets to enter streams where the parasites reproduce. These manipulated crickets become a substantial food subsidy for stream fishes. We used a field experiment to investigate how this subsidy affects the stream community and ecosystem function. When crickets were available, predatory fish ate fewer benthic invertebrates. The resulting release of the benthic invertebrate community from fish predation indirectly decreased the biomass of benthic algae and slightly increased leaf break-down rate. This is the first experimental demonstration that host manipulation by a parasite can reorganise a community and alter ecosystem function. Nematomorphs are common, and many other parasites have dramatic effects on host phenotypes, suggesting that similar effects of parasites on ecosystems might be widespread.

Fusion genes involving have recently been identified in precursor B-cell acute lymphoblastic leukemia, mutually exclusive of the common risk stratifying genetic abnormalities, although their true incidence and associated clinical characteristics remains unknown. We identified 16 acute lymphoblastic leukemia cases and 1 lymphoma case harboring fusions, including (n=10), (n=6) and one novel fusion. The incidence of fusions overall was 2.4% among consecutive B-cell acute lymphoblastic leukemia patients enrolled onto a single clinical trial. They frequently showed a cytoplasmic μ chain-positive pre-B immunophenotype and often expressed an aberrant CD5 antigen. Besides up- and down-regulation of and, elevated expression was also a characteristic feature of fusions-positive patients. Mutations of , recurrent in T-cell acute lymphoblastic leukemia, also showed an unexpectedly high frequency (50%) in these patients. fusion-positive patients were older (median age 9 years) with elevated WBC counts (median: 27,300/μl) at presentation, and, as a result, were mostly classified as NCI high-risk. Although they responded well to steroid treatment, fusion-positive patients showed a significantly worse outcome, with 53.3% relapse and subsequent death. Stem cell transplantation was ineffective as a salvage therapy. Interestingly, relapse was frequently associated with the presence of gene deletions. Our observations indicate that fusions comprise a distinct subgroup of precursor B-cell acute lymphoblastic leukemia with a characteristic immunophenotype and gene expression signature, associated with distinct clinical features.

Microbiome dynamics are both crucial indicators and drivers of human health, agricultural output, and industrial bio-applications. However, predicting microbiome dynamics is notoriously difficult because communities often show abrupt structural changes, such as dysbiosis in human microbiomes. We here integrate theoretical and empirical bases for anticipating drastic shifts of microbial communities. We monitored 48 experimental microbiomes for 110 days and observed that various community-level events, including collapse and gradual compositional changes, occurred according to a defined set of environmental conditions. We then confirmed that the abrupt community changes observed through the time-series could be described as shifts between alternative stable states or dynamics around complex attractors. Furthermore, collapses of microbiome structure were successfully anticipated by means of the diagnostic threshold defined with the energy landscape analysis of statistical physics or that of a stability index of nonlinear mechanics. These results indicate that abrupt microbiome events in complex microbial communities can be forecasted by extending classic ecological concepts to the scale of species-rich microbial systems.

B cells can differentiate into the antibody-secreting cells, plasma cells, whereas the crucial signals that positively control the entry into the pathway to plasma cells have been unclear. Triggering via CD27 by CD27 ligand (CD70) on purified peripheral blood B cells yielded an increase in the number of plasma cells in the presence of interleukin-10 (IL-10). Differentiation into plasma cells by a combination of IL-10 and CD70 transfectants occurred in CD27+ B cells but not in CD27− B cells. Moreover, addition of IL-2 to the IL-10 and CD70-transfect activation system greatly induced differentiation into plasma cells. In the presence of only IL-2, IL-4, or IL-6, CD70 transfectants did not promote differentiation into plasma cells. On the other hand, CD40 signaling increased the expansion of a B-cell pool from peripheral blood B cells primarily activated by IL-2, IL-10, and anti-CD40 monoclonal antibody (MoAb). Finally, CD27 signaling also rescued B cells from IL-10–mediated apoptosis. These data demonstrate that CD27 ligand (CD70) is a key molecule to prevent the IL-10–mediated promotion of apoptosis and to direct the differentiation of CD27+ memory B cells toward plasma cells in cooperation with IL-10.