Although B cells expressing the IFNγR or the IFNγ-inducible transcription factor T-bet promote autoimmunity in Systemic Lupus Erythematosus (SLE)-prone mouse models, the role for IFNγ signaling in human antibody responses is unknown. We show that elevated levels of IFNγ in SLE patients correlate with expansion of the T-bet expressing IgDnegCD27negCD11c+CXCR5neg (DN2) pre-antibody secreting cell (pre-ASC) subset. We demonstrate that naïve B cells form T-bethi pre-ASCs following stimulation with either Th1 cells or with IFNγ, IL-2, anti-Ig and TLR7/8 ligand and that IL-21 dependent ASC formation is significantly enhanced by IFNγ or IFNγ-producing T cells. IFNγ promotes ASC development by synergizing with IL-2 and TLR7/8 ligands to induce genome-wide epigenetic reprogramming of B cells, which results in increased chromatin accessibility surrounding IRF4 and BLIMP1 binding motifs and epigenetic remodeling of IL21R and PRDM1 loci. Finally, we show that IFNγ signals poise B cells to differentiate by increasing their responsiveness to IL-21.

Over 30 years ago, receptors for the Fc region of IgG (FcgR) were implicated in the pathogenesis of systemic lupus erythematosus (SLE). Since those pioneering studies, our knowledge of the structure and function of these FcgRs has increased dramatically. We now know that FcgR contributes to the regulation of acquired immunity and to the regulation of innate immune responses where FcgRs act as specific receptors for innate opsonins (CRP and SAP). Our understanding of the genomic architecture of the genes encoding the FcgR has also witnessed remarkable advances. Numerous functionally relevant single-nucleotide polymorphism (SNP) variants and copy number (CN) variants have been characterized in the FcgR genes. Many of these variants have also been shown to associate with risk to development of SLE and some have been associated with disease progression. This review will provide an overview of the FcgR in relation to SLE, including consideration of the role of genetic variants in FcgR in SLE pathogenesis. The difficulties in assessing genetic variation in these genes will be discussed. To enhance our understanding of the functional roles of these receptors in SLE, future research will need to integrate our knowledge of SNP variants, CN variants and the functional diversity of these receptors.

BackgroundMycoplasma pneumoniae is a common pathogen that causes upper and lower respiratory tract infections in people of all ages, responsible for up to 40 % of community-acquired pneumonias. It also causes a wide array of extrapulmonary infections and autoimmune phenomena. Phylogenetic studies of the organism have been generally restricted to specific genes or regions of the genome, because whole genome sequencing has been completed for only 4 strains. To better understand the physiology and pathogenicity of this important human pathogen, we performed comparative genomic analysis of 15 strains of M. pneumoniae that were isolated between the 1940s to 2009 from respiratory specimens and cerebrospinal fluid originating from the USA, China and England.ResultsIllumina MiSeq whole genome sequencing was performed on the 15 strains and all genome sequences were completed. Results from the comparative genomic analysis indicate that although about 1500 SNP and indel variants exist between type1 and type 2 strains, there is an overall high degree of sequence similarity among the strains (>99 % identical to each other). Within the two subtypes, conservation of most genes, including the CARDS toxin gene and arginine deiminase genes, was observed. The major variation occurs in the P1 and ORF6 genes associated with the adhesin complex. Multiple hsdS genes (encodes S subunit of type I restriction enzyme) with variable tandem repeat copy numbers were found in all 15 genomes.ConclusionsThese data indicate that despite conclusions drawn from 16S rRNA sequences suggesting rapid evolution, the M. pneumoniae genome is extraordinarily stable over time and geographic distance across the globe with a striking lack of evidence of horizontal gene transfer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1801-0) contains supplementary material, which is available to authorized users.

Highlights d Chemogenetic and/or optogenetic activation of primary cilia alters axonal behavior d Ciliary activity modulates axonal growth cones and filopodiallamellipodial balance d Arl13b-Inpp5e activity in cilia facilitates axonal tract formation and targeting d Disrupted ciliary signaling contributes to axonal tract malformations in JSRD

The intestinal microbiome in early life influences development of the mucosal immune system and predisposition to certain diseases. Because less is known about the microbiome in the stomach and its relationship to disease, we characterized the microbiota in the stomachs of 86 children and adults and the impact of H. pylori infection on the bacterial communities. The overall composition of the gastric microbiota in children and adults without H. pylori infection was similar, with minor differences in only low abundance taxa. However, the gastric microbiota in H. pylori-infected children, but not infected adults, differed significantly in the proportions of multiple high abundance taxa compared with their non-infected peers. The stomachs of H. pylori-infected children also harbored more diverse microbiota, smaller abundance of Firmicutes, and larger abundances of non-Helicobacter Proteobacteria and several lower taxonomic groups than stomachs of H. pylori-infected adults. Children with restructured gastric microbiota had higher levels of FOXP3, IL10 and TGFβ expression, consistent with increased T regulatory cell responses, compared with non-infected children and H. pylori-infected adults. The gastric commensal bacteria in children is altered during H. pylori infection in parallel with more tolerogenic gastric mucosae, potentially contributing to the reduced gastric disease characteristic of H. pylori-infected children.