Mice that lack either CD40 (expressed on B cells) or CD40 ligand (expressed on activated T cells) are able neither to make IgG, IgA or IgE antibody responses, nor to generate germinal centres (the sites of formation of memory B cells). It has been assumed that these lesions were the result of an absence of signals to B cells through CD40. Here we show that the failure to signal T cells through CD40 ligand is an important contributory cause. Administration of soluble CD40 in vivo to CD40 knockout mice, restoring the missing signal through CD40 ligand initiates germinal centre formation. Furthermore, T cells primed in the absence of CD40 (in CD40 knockout mice) are unable to help normal B cells to class switch or to form germinal centres (GC). These results indicate that co-stimulation of T cells through CD40 ligand causes their differentiation into cells that help B cells to make mature antibody responses and to generate memory populations.

LINE-1 (L1) retrotransposons represent approximately one sixth of the human genome, but only the human-specific L1HS-Ta subfamily acts as an endogenous mutagen in modern humans, reshaping both somatic and germline genomes. Due to their high levels of sequence identity and the existence of many polymorphic insertions absent from the reference genome, the transcriptional activation of individual genomic L1HS-Ta copies remains poorly understood. Here we comprehensively mapped fixed and polymorphic L1HS-Ta copies in 12 commonly-used somatic cell lines, and identified transcriptional and epigenetic signatures allowing the unambiguous identification of active L1HS-Ta copies in their genomic context. Strikingly, only a very restricted subset of L1HS-Ta loci - some being polymorphic among individuals - significantly contributes to the bulk of L1 expression, and these loci are differentially regulated among distinct cell lines. Thus, our data support a local model of L1 transcriptional activation in somatic cells, governed by individual-, locus-, and cell-type-specific determinants.DOI: http://dx.doi.org/10.7554/eLife.13926.001