Properties of IL-21/IL-21R and its regulation of B lymphocytes

IL-21 is a member of the common gamma chain (gammac)-dependent cytokine family that mediates its cellular effects through the functional receptor that consists of gammac and IL-21Ralpha chain. However, the regulation of the IL-21Ralpha chain has not been precisely defined. The most important effect of IL-21 is to cooperatively with IL-4 promote T cell-dependent Ab responses. Paradoxically, IL-21 has been shown to deliver pro-apoptosic signals and variably support B cell proliferation in vitro. Moreover, it was unclear how IL-21 and IL-4, both produced by activated T cells, individually and jointly influence B cell responses.Using a novel mAb to IL-21R, the IL-21R was detected during T and B cell development such that this receptor is expressed by all mature lymphocytes. The IL-21R was further regulated during peripheral B cell development and upregulated after B and T activation. Functional studies demonstrated that IL-21 substantially inhibited proliferation and induced Bim-dependent apoptosis for LPS or CpG DNA-activated B cells. In contrast, IL-21 induced both co-stimulation and apoptosis for anti-CD40 stimulated B cells whereas IL-21 primarily co-stimulated B cells activated by anti-IgM or anti-IgM plus anti-CD40. Upon blocking apoptosis using C57BL/6 Bim-deficient or Bcl-2 transgenic B cells, IL-21 readily co-stimulated responses to anti-CD40 while proliferation to LPS was still inhibited. Engagement of CD40 prevented the inhibitory effect by IL-21 for LPS-activated B cells. IL-4 exhibited redundancy with IL-21 in regulating B cell survival, proliferation, IgG1 class switching and secretion. Nevertheless, these two cytokines showed distinct functions. IL-21 decreased the expression of CD23 and CD44 while IL-4 increased their expression on activated B cells. IL-21 but not IL-4 sustained the expression of CD138, a plasma cell marker, at a later phase of the B cell response.Collectively, these data indicate that there are three separable outcomes for IL-21 and/or IL-4-stimulated B cells, apoptosis, growth arrest, or co-stimulation. We favor a model where these cytokines promote B cell maturation during a productive T cell-dependent B cell response while favoring growth arrest and apoptosis for non-specifically or inappropriately activated B cells. Furthermore, their distinctive activities may instruct post-germinal center B cells to enter separate differentiation pathways.</p

Membranes with Intrinsic Micro-Porosity: Structure, Solubility, and Applications

Microporous polymer membranes have been widely studied because of their excellent separation performance. Among them, polymers of intrinsic micro-porosity (PIMs) have been regarded as a potential next-generation membrane material for their ultra-permeable characteristics and their solution-processing ability. Therefore, many reviews have been reported on gas separation and monomers for the preparation of PIMs. This review aims to provide an overview of the structure-solubility property. Different structures such as non-network and network macromolecular structure made of different monomers have been reviewed. Then their solubility with different structures and different separation applications such as nanofiltration, pervaporation, and gas/vapor separation are summarized. Lastly, we also provide our perspectives on the challenges and future directions of the microporous polymer membrane for the structure-property relationship, anti-physical aging, and more

Redundant and unique regulation of activated mouse B lymphocytes by IL‐4 and IL‐21

IL‐21 distinctively regulates B cell growth and death, and it redundantly functions with IL‐4 for IgG production. B cells likely encounter IL‐4 and IL‐21 in vivo, as both are secreted by activated T cells. Therefore, the action of both these cytokines was investigated during activation of B cells. IL‐21 or the combination of IL‐4 and IL‐21 inhibited proliferation by purified mouse B cells to LPS or CpG DNA, whereas these cytokines enhanced proliferation after engaging the BCR or CD40. Although B cell subsets expressed somewhat varied levels of the IL‐21 receptor, LPS‐stimulated follicular and marginal B cell subsets were also dominantly susceptible to IL‐21‐induced growth arrest and cell death. After activation of B cells with CD40 and LPS, IL‐4 and IL‐21 distinctively regulated the expression of CD23, CD44, and CD138, and they cooperatively promoted IgG1 class‐switching and synthesis. These findings support a model in which the presence of IL‐4 and IL‐21 inhibits B cells activated by polyclonal innate signals, and they promote B cell expansion and differentiation during T cell‐dependent antibody responses, although the individual responses to IL‐4 and IL‐21 do not always overlap

Fabrication of high silicalite-1 content filled PDMS thin composite pervaporation membrane for the separation of ethanol from aqueous solutions

Sedimentation of silicalite-1 occurs in the fabrication of thin silicalite-1 filled polydimethylsiloxane (PDMS) hybrid composite membranes if the viscosity of membrane solution is low, which makes this preparation challenging. In this work, a new method that use a platinum catalytic agent to assist the pre-polymerization of PDMS polymer to increase the viscosity of the membrane solution was studied. With this method, supported silicalite-1 filled PDMS hybrid composite membranes were fabricated and applied in the pervaporative separation of a 5 wt% dilute ethanol aqueous solution. The effect of the concentration of platinum catalytic agent on the membrane properties was first investigated using CRM, DSC and extraction experiment. Optimum of viscosity of the composite membrane solution was then conducted and a selective layer of as thin as 5 gm thickness was obtained with a flux of 5.52 kg/m(2)h in combination with a separation factor of 15.5 at 50 degrees C. After that the separation performances of different thick membranes, interfacial adhesion properties of hybrid membranes, comparisons with other reported results and membrane stability were investigated. Results showed homemade silicalite-1-PDMS hybrid composite membrane offers relatively high separation performance, indicating a potential industrial application for the separation of ethanol from aqueous solutions.</p

Distinct Activation Signals Determine whether IL-21 Induces B Cell Costimulation, Growth Arrest, or Bim-Dependent Apoptosis

IL-21 costimulates B cell proliferation and cooperatively with IL-4 promotes T cell-dependent Ab responses. Somewhat paradoxically, IL-21 also induces apoptosis of B cells. The present study was undertaken to more precisely define the expression of the IL-21R, using a novel mAb, and the circumstances by which IL-21 promotes B cell growth vs death. The IL-21R was first detected during T and B cell development, such that this receptor is expressed by all mature lymphocytes. The IL-21R was further up-regulated after B and T activation, with the highest expression by activated B cells. Functional studies demonstrated that IL-21 substantially inhibited proliferation and induced Bim-dependent apoptosis for LPS or CpG DNA-activated B cells. In contrast, IL-21 induced both costimulation and apoptosis for anti-CD40-stimulated B cells, whereas IL-21 primarily costimulated B cells activated by anti-IgM or anti-IgM plus anti-CD40. Upon blocking apoptosis using C57BL/6 Bim-deficient or Bcl-2 transgenic B cells, IL-21 readily costimulated responses to anti-CD40 while proliferation to LPS was still inhibited. Engagement of CD40 or the BCR plus CD40 prevented the inhibitory effect by IL-21 for LPS-activated B cells. Collectively, these data indicate that there are three separable outcomes for IL-21-stimulated B cells: apoptosis, growth arrest, or costimulation. We favor a model in which IL-21 promotes B cell maturation during a productive T cell-dependent B cell response, while favoring growth arrest and apoptosis for nonspecifically or inappropriately activated B cells

Clinical features of Chinese patients with Fuchs' syndrome

To characterize the clinical features of Chinese patients with Fuchs' syndrome. Retrospective noncomparative case series. One hundred eighteen eyes of 104 consecutive patients with Fuchs' syndrome initially examined between January 1999 and March 2005. The history and clinical findings of all consecutive Fuchs' patients attending the Zhongshan Ophthalmic Center were reviewed. Auxiliary examinations, including laser flare-cell photometry, ultrasound biomicroscopy (UBM), fundus fluorescein angiography (FFA), and serologic tests for Toxoplasma gondii, were performed in certain cases. Patients' demographics, clinical presentation, and auxiliary examination findings. One hundred four patients (49 male, 55 female) were included in this study. Unilateral involvement was noted in 90 patients (86.5%). The most common symptom was blurred or decreased vision (86%). Stellate and medium-sized keratic precipitates (KPs) were noted in 108 eyes (91.5%). A mild anterior chamber (AC) reaction was observed in all the affected eyes. Heterochromia was observed in only 15 affected eyes, although there were varying degrees of iris depigmentation in all patients. Iris nodules, mostly Koeppe, were present in 28.0% of the affected eyes. Complicated cataract, vitreous opacity, and secondary glaucoma were observed in 84 of 118 eyes (70.7%), 31 eyes of 42 eyes (73.8%), and 24 of 118 eyes (23.1%), respectively. The mean laser flare photometry value (6.4+/-2.3 photon counts per millisecond) and the cell number in the AC (1.5+/-1.2 cells per 0.5 mm3) in 25 patients were both significantly higher than those in 25 healthy controls (5.3+/-2.3 photon counts per millisecond and 0.8+/-0.6 cells per 0.5 mm3) (P <0.05). Ultrasound biomicroscopy revealed exudates adjacent to the ciliary body in 18 of 24 patients (75%). Serological tests failed to confirm an association of Fuchs' syndrome with toxoplasmosis. Retinal capillary leakage in the midperipheral fundus and disc staining at the late stage were observed in most of the eyes examined by FFA. Fuchs' syndrome in Chinese patients is characterized by a mild uveitis with characteristic KPs, varying degrees of iris depigmentation, and, occasionally, heterochromia. Exudates adjacent to the ciliary body and subclinical retinal and optic nerve involvement were common in the patients who were studied by UBM and FF

Quantitative assessment concerning the contribution of IL-2R beta for superantigen-mediated T cell responses in vivo

IL-2- and IL-2R-deficient mice readily develop T cell-dependent immune responses in vivo, but the relevance of this finding is complicated by severe concurrent autoimmunity. Furthermore, the detection of such responses does not address whether under normal circumstances IL-2 dominates T cell immunity. In the present report, we investigated the extent IL-2-independent T cell growth is mediated by other cytokines in the IL-2 family and compared such responses to those generated by IL-2/IL-2R-sufficient T cells. T cell expansion and contraction to the superantigen staphylococcal enterotoxin A (SEA) by autoimmune-free IL-2R beta super(-/-) CD4 and CD8 T cells were comparable to normal control mice, although their CD8 super(+) T cells did not optimally develop into IFN gamma -producing effector cells. The proliferation by these IL-2R beta -deficient T cells in vivo was independent of IL-2, IL-4 and IL-15 and not blocked by mAbs to the common gamma chain. However, in co-adoptive transfer experiments, wild-type T cells exhibited somewhat more extensive proliferation than IL-2R beta -deficient T cells to SEA and this difference was almost entirely accounted for by CD8 super(+) T cells. Collectively, these data indicate that substantial T cell proliferation occurs in the absence of responsiveness to cytokines in the IL-2 family, although maximal T cell proliferation and development of IFN gamma -producing effector CD8 super(+) T cells depend upon IL-2R beta