Infection with Staphylococcus aureus does not induce long-lived protective immunity for reasons that are not completely understood. Human and murine vaccine studies support a role for antibodies in protecting against recurring infections, but S. aureus modulates the B cell response through expression of Staphylococcal Protein A (SpA), a surface protein that drives polyclonal B cell expansion and induces cell death in the absence of co-stimulation. In this murine study, we show that SpA altered the fate of plasmablasts and plasma cells (PCs) by enhancing the short-lived extrafollicular response and reducing the pool of bone marrow (BM)-resident long-lived PCs (LLPCs). The absence of LLPCs was associated with a rapid decline in antigen-specific, class-switched antibody. In contrast, when previously inoculated mice were challenged with isogenic Δspa S. aureus, cells proliferated in the BM survival niches and sustained long-term antibody titers. The effects of SpA on PC fate were limited to the secondary response, as antibody levels and the formation of B cell memory occurred normally during the primary response in mice inoculated with either WT or Δspa S. aureus. Thus, failure to establish long-term protective antibody titers against S. aureus was not a consequence of diminished formation of B cell memory; instead, SpA reduced the proliferative capacity of PCs that entered the BM, diminishing the number of cells in the long-lived pool.

The impact of potential game-changing advances in treatment can only be maximised with parallel advances in the diagnostic landscape for DR-TB. Speed and accuracy of DR-TB diagnosis has been boosted by the rollout of rapid molecular testing, but this new technology doesn't fill every gap in the complex diagnostic algorithm required to diagnose DR-TB. Scale up of an optimal package of diagnostic technologies and services will be a critical factor in reversing today's trends where people die while waiting for a proper diagnosis or are given sub-optimal treatment. Read MSF's brief, Beyond the Microscope: addressing the critical need for TB diagnostics,

Memory B cell responses are vital for protection against infections, but must also be regulated to prevent autoimmunity. Cognate T cell help, somatic hypermutation, and affinity maturation within germinal centers (GCs) are required for high affinity memory B cell formation; however, the signals that commit GC B cells to the memory pool remain unclear. In this study, we identify a role for IgG immune complexes (ICs), FcγRs, and BAFF during the formation of memory B cells in mice. We found that early secretion of IgG in response to immunization with a T-dependent antigen leads to IC-FcγR interactions that induce DCs to secrete BAFF which acts at or upstream of Bcl-6 in activated B cells. Loss of CD16, hematopoietic cell-derived BAFF, or blocking IC:FcγR regions in vivo diminished the expression of Bcl-6, the frequency of GC and memory B cells, and secondary antibody responses. BAFF also contributed to the maintenance and/or expansion of the Tfh population, although it was dispensable for their formation. Thus, early antibody responses contribute to the optimal formation of B cell memory through IgG-ICs and BAFF. Our work defines a new role for FcγRs in GC and memory B cell responses.

No abstract

hen Lydia Alvarez-Erviti started her postdoctoral studies at the University of Oxford, UK, in 2008, her goal was to develop gene therapies for neurodegenerative diseases. She had identified her target-α-synuclein, a protein that accumulates in the brains of people with Parkinson's disease-and designed a short interfering RNA (siRNA) to reduce the amount of α-synuclein made in mice. But she needed to get the siRNA into the brain. The method would have to protect the RNA, cross the barrier between circulating blood and the brain, and be safe enough to use repeatedly. Fortuitously, a colleague had begun studying something that could work-naturally occurring, nano-sized vesicles called exosomes. Exosomes are 30-100-nanometre-wide