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Lineage development is accompanied by specification of gene expression. Murre and colleagues show that during B cell development, many genes relocate in the nucleus, driven by chromatin-looping interactions with transcription factors.
How IL-17 signaling is regulated remains poorly understood. Dong and colleagues identify the ubiquitin-specific protease USP25 as a negative regulator of IL-17-mediated signaling and inflammation.
Signaling through toll-like receptors induces cytokines and type I interferon. Moynagh and colleagues show that the E3 ubiquitin ligase Pellino3 specifically represses the expression of type I interferon in response to TLR3 activation.
By comparing gene-expression profiles, Randolph and colleagues distinguish different types of macrophages and pinpoint the differences between macrophages and dendritic cells.
How isotype-specific immunoglobulin production is regulated is largely unknown. Sun and colleagues show that the kinase TBK1 acts as a negative regulator of IgA class switching by attenuating NIK-mediated NF-κB signaling.
TLR4 signaling shifts from plasma membrane TIRAP-MyD88–mediated pathways to endosomal TRAM-TRIF–mediated signaling. Vanhaesebroeck and colleagues show that the kinase PI(3)K p110δ is required for TLR4 internalization and degradation of TIRAP.
Successful pathogens can overcome innate immune defenses. Ge and colleagues show that Tir protein expressed by enteropathogenic Escherichia coli is injected into host cells, where it interferes with adaptor TRAF6–dependent signaling.
The regulator c-Myc is well known for controlling cell growth but, paradoxically, evidence for its involvement in germinal centers has proven elusive. Rajewsky and colleagues show that it is essential for their development and maintenance.
The molecular control of germinal center selection is still being determined. Dalla-Favera and colleagues show that the cell-cycle regulator c-Myc is essential for B cell selection and reentry into the germinal center.