Differences in immune responses to viruses and autoimmune diseases such as systemic lupus erythematosus (SLE) can show sexual dimorphism. Age-associated B cells (ABC) are a population of CD11c+T-bet+ B cells critical for antiviral responses and autoimmune disorders. Absence of DEF6 and SWAP-70, two homologous guanine exchange factors, in double-knock-out (DKO) mice leads to a lupus-like syndrome in females marked by accumulation of ABCs. Here we demonstrate that DKO ABCs show sex-specific differences in cell number, upregulation of an ISG signature, and further differentiation. DKO ABCs undergo oligoclonal expansion and differentiate into both CD11c+ and CD11c− effector B cell populations with pathogenic and pro-inflammatory function as demonstrated by BCR sequencing and fate-mapping experiments. Tlr7 duplication in DKO males overrides the sex-bias and further augments the dissemination and pathogenicity of ABCs, resulting in severe pulmonary inflammation and early mortality. Thus, sexual dimorphism shapes the expansion, function and differentiation of ABCs that accompanies TLR7-driven immunopathogenesis.

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The aetiological agent of amphibian chytridiomycosis Batrachochytrium dendrobatidis is a primary cause of amphibian population declines. Current surveillance is based on the detection of B. dendrobatidis in its host but in vitro work suggests infective stages may survive in the abiotic environment for at least 3 mo. We describe here a surveillance system using filtration and quantitative PCR that can detect B. dendrobatidis in small (<1 l) volumes of water. After assessing the analytical sensitivity of the protocol for both water and sediment samples in the laboratory, we analyzed environmental samples from the Sierra de Guadarrama mountain range in Spain at locations associated with chytrid-related die-offs and at other sites across Spain. B. dendrobatidis was detected in samples from 64% of the ponds in the Sierra de Guadarrama and at 2 sites outside this region, showing that levels of amphibian exposure to B. dendrobatidis are spatially heterogeneous. In experimental microcosms, we detected B. dendrobatidis for up to 12 wk, though we found no evidence for an overall increase in biomass. Our results emphasise the need to further investigate the life cycle of B. dendrobatidis to more completely understand the epidemiology of this emerging pathogen. KEY WORDS: Chytridiomycosis · Batrachochytrium dendrobatidis · Environmental surveillance · Filtration Resale or republication not permitted without written consent of the publisherDis Aquat Org 77: [105][106][107][108][109][110][111][112] 2007 solid culture media (Longcore et al. 1999). Thus, zoospores may persist in the environment for long periods of time and there may be hitherto undetected saprophytic stages with the ability to multiply. To better understand the biology and to analyze the epidemiology of B. dendrobatidis, a technique that can detect the pathogen in the environment and outside the host is urgently required.Traditionally, zoosporic fungi are isolated with baiting methods using the bait a substrate for the fungus (Fuller 1987). This technique works well if the objective is to characterize an unknown fungal community, but is less effective if the objective is to isolate a particular species, especially if the target species is found at low densities or is poorly competitive. Previous attempts to obtain environmental samples of Batrachochytrium dendrobatidis by using traditional baiting techniques were not successful (Longcore et al. 1999, Livo, 2004.The screening of DNA samples with environmental quantitative PCR provides a powerful tool to quantitatively detect water-and soil-borne pathogens, and its applications have been demonstrated for pathogenic Candida cells (Brinkman et al. 2003) and for Perkinsus marinus, a serious pathogen of the oyster Crassostrea virginica (Audemard et al. 2004). Here, we describe the development of a method that combines a simple, hand-held filtration system, a commercially available DNA extraction kit and a highly sensitive quantitative real-time PCR assay to detect B. dendrobatidis in small volumes (<1 l)...

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Multiple markers were used to count Langerhans' cells in the cervix. In the normal cervix, thymocyte antigen (T6) and adenosine triphosphatase ( ATPase) demonstrated the largest population of Langerhans' cells. MHC Class 11 positive cells were equivalent to 60%, and SlOO positive cells were equivalent to 35% of T6 or ATPase positive cells, Whereas Langerhans' cells demonstrated by T6, ATPase, and MHC Class I1 antigen were evenly distributed throughout the epithelium, the SlOO positive cells were seen predominantly near lymphocytic aggregates and capillaries. In human papillomavirus infection and cervical intraepithelial neoplasia the numbers of T6, ATPase, or MHC Class I1 positive Langerhans' cells were reduced by 60% but the SlOO positive cells were almost completely depleted. These findings suggested that there were different subpopulations of Langerhans' cells in the cervical epithelium. The depletion of Langerhans' cells, particularly the selective depletion of the SlOO positive subpopulation, might cause a localized immunodeficiency that impairs immune surveillance and the cell-mediated immune response to human papillomavirus infection and cervical intraepithelial neoplasia.Human papillomavirus (HPV), types 16 and 18in particular, appears to be an important aetiological factor in the development of cervical neoplasia (Gissman ef al. 1983;McCance et al. 1985; Kreider et al. 1985). Viral pathogenesis is the outcome of interaction between the virulence of the virus and the host immune

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Age-associated B cells (ABCs) have emerged as critical components of immune responses. Their inappropriate expansion and differentiation have increasingly been linked to the pathogenesis of autoimmune disorders, aging-associated diseases, and infections. ABCs exhibit a distinctive phenotype and, in addition to classical B cell markers, often express the transcription factor T-bet and myeloid markers like CD11c; hence, these cells are also commonly known as CD11c + T-bet + B cells. Formation of ABCs is promoted by distinctive combinations of innate and adaptive signals. In addition to producing antibodies, these cells display antigen-presenting and proinflammatory capabilities. It is becoming increasingly appreciated that the ABC compartment exhibits a high degree of heterogeneity, plasticity, and sex-specific regulation and that ABCs can differentiate into effector progeny via several routes particularly in autoimmune settings. In this review, we will discuss the initial insights that have been obtained on the molecular machinery that controls ABCs and we will highlight some of the unique aspects of this control system that may enable ABCs to fulfill their distinctive role in immune responses. Given the expanding array of autoimmune disorders and pathophysiological settings in which ABCs are being implicated, a deeper understanding of this machinery could have important and broad therapeutic implications for the successful, albeit daunting, task of targeting these cells.