This suggested that cross-linking of NKG2D was sufficient for rejection of ligand-expressing tumor cell lines. Ab blocking of NKG2D inhibited cytotoxicity against NKG2D-L-expressing tumor cells indicating a direct activating rather than a costimulating function of NKG2D 18. However, a possible role of other ligands could BTK animal study not be excluded in these studies. Direct evidence for a role of NKG2D receptors in tumor surveillance was provided by a recent study where onset of spontaneous malignancies

was accelerated when mice were devoid of NKG2D expression 19. Likewise, it has not been clearly defined if MHC class I-mediated signals are necessary or sufficient for NK-cell activity. In primary leukemias, lack of inhibition was not sufficient to confer cytotoxicity 20, but cell lines were rendered NK-resistant by HLA-C transfection, thus indicating a requirement of MHC class I down-regulation for NK-cell activity 21. On the other hand, cells displaying normal levels of MHC class I were susceptible to NK-cell lysis if effector cells became otherwise activated 22, 23. A clue to an understanding of these data might be a two-signal

requirement of NK-cell activation. In resting but not pre-activated NK cells, NKG2D was identified as a coactivation signal that needed coengagement of other receptors, such as 2B4 and natural cytotoxicity Temsirolimus receptors (NCR) 24. In another study, NK-dependent lysis of some tumors was only dependent

on NCR, whereas in other tumors, synergistic Erastin molecular weight effects of NCR and NKG2D were found 25. Recently, a sequential NK-cell activation process was proposed 26. In this model, activation of resting NK cells required a priming signal that was provided by IL-2 or by unknown ligands of tumor cells independently of IL-2, and a subsequent triggering event that was mediated by CD69. MHC class I down-regulation was not needed for tumor-induced NK activity in this study 26. Resistance of tumors might either arise through a lack of priming of NK cells (type 1 evasion) or by the inability of the tumor to deliver triggering signals to already primed NK cells (type 2 evasion) 26. Reports suggesting a two-signal requirement for NK-cell activation were only based on in vitro studies, and the role of NKG2D that was described as an NCR in earlier studies 27, 28 was not addressed in the context of the two-stage model 26. We were therefore interested in the mechanisms of NK-cell activation in tumor surveillance in vivo and we specifically investigated the role of “missing self” and of NKG2D/ligand interactions as well as the mechanisms underlying tumor escape. We previously showed that missing self can induce strong and protective NK-cell responses in a tumor transplantation model 6, but this may not reflect the situation in endogenous tumors.

apiosperma/P. boydii complex, which could not be distinguished morphologically. False negative reactions may be due to PCR inhibition. Since no plasmid was used as internal control in DNA extraction, PCR inhibition could not be excluded. When DNA dilutions were used, PCR-RLB remained negative, suggesting that no Scedosporium DNA was present. Some of the culture negative results with positive PCR-RLB might be explained by preceding azole treatment or by the presence GSI-IX research buy of non-vital fungal elements. Twenty-five sputum samples

were obtained from CF patients undergoing antifungal treatment, eight of these (32%) were positive for Scedosporium using PCR-RLB. This deviates only marginally from the degree of positive molecular

results in the global population (29/110, or 26.4%). Some species have phenetic features such as S. aurantiacum excuding a yellow pigment, and S. prolificans inflated bases of conidiogenous cells. In contrast, P. apiosperma, S. dehoogii, P. boydii and P. minutispora are almost indistinguishable morphologically. The PCR-RLB provides insight into the species spectrum, P. apiosperma JNK inhibitor being the most common with 20 isolates, followed by P. boydii (17), S. aurantiacum (6), P. minutispora (1) and S. prolificans (1). Scedosporium dehoogii, which is common in the environment and is supposed to have low virulence,11 was not encountered in our study and thus also appears to be a poorer pulmonary coloniser. The species spectrum involved in colonisation of the airways in CF patients thus shows large clinical differences between sibling Scedosporium species. In conclusion, the PCR-RLB assay applied in this study allows sensitive and specific simultaneous detection and identification of P. apiosperma/P. boydii complex, which contributes to a major improvement in the screening of P. apiosperma/P. boydii colonisation in CF patients. The method, however, needs validation by an analysis of the presence

of Scedosporium DNA or non-viable cells in air and airways. This work was funded by Special Scientific Research Project and Public Welfare Project of Health Profession of China, 11th Five-year key special subject for Sci & Tech Research of China and China Scholarship Council. We gratefully acknowledge Anneke Bergmans in the Laboratory of Medical Microbiology www.selleck.co.jp/products/Y-27632.html at Franciscus Hospital, Roosendaal, the Netherlands, for helpful discussions on PCR-RLB. The work was carried out in cooperation with the ECMM-ISHAM working group on Pseudallescheria and Scedosporium infections and with the ISHAM working group on Fungal respiratory infections in Cystic Fibrosis (Fri-CF). No conflict of interests declared. “
“The objective of this study was to compare phospholipase production between fluconazole-resistant and fluconazole-susceptible strains of Candida albicans in order to explore the relationship between resistance to antifungal drugs and virulence of C. albicans.

[33] However, cellular and molecular as well as genetic mechanisms underlying the pathogenesis of FCD type II are largely unknown. Currently, FCD is a heterogeneous group of disorders commonly associated with medically intractable epilepsy mainly in children. The cellular pathology of FCD can be stratified depending on whether or not certain specific microscopic abnormalities are noted in a given specimen. Mischel et al[54] reviewed over 70 examples of cortical dysplasia from young patients who underwent hemispherectomy or lobectomy, and the following eight major histopathologic

features were scored as being present or absent in each specimen: (i) cortical laminar disorganization (a defining feature of cortical dysplasia and hence present in all specimens) (Fig. 7); (ii) single heterotopic neurons within the deep white matter Galunisertib in vitro or molecular layer (layer I) of the cortex (94.4%); (iii) neuronal cytomegaly (63.9%); (iv) neuronal cytoskeletal abnormalities;[69] (55.6%) (v) macroscopically visible neuronal heterotopias, usually Alectinib concentration in the subcortical white matter (40.3%); (vi) foci of polymicrogyria (PMG) (13.9%); (vii) neuroglial excrescences in the subarachnoid space (13.9%); and (viii) BCs (18.1%). Based on the presence or absence of various combinations of these histologic

features, individual cases were subclassified as being mild, moderate or severe in the first proposed grading system (Table 4).[54] Preliminary correlation of the severity of cortical dysplasia with clinical severity of the seizure disorder has shown that

mean preoperative seizure frequency correlated well with the histologic grade, and children with moderate or severe degrees of cortical dysplasia were more likely to have shown a preoperative neurologic deficit. Another study on cortical dysplasia cases in the UCLA pediatric and adult epilepsy surgery cohort N-acetylglucosamine-1-phosphate transferase (n = 97) determined nine histopathologic elements, including: (i) cortical disorganization and dyslamination as an essential feature of cortical dysplasia; (ii) excessive heterotopic white matter neurons (99%); (iii) dysmorphic-cytomegalic neurons (52%); (iv) BCs (40%); (v) excessive heterotopic neurons in the cortical molecular layer (40%); (vi) marginal and nodular glioneuronal heterotopia (30%); (vii) polymicrogyria (27%); (viii) immature neurons (15%); and (ix) persistence of the subpial or superficial granular cell layer (8%).[70] Histograms of the frequency of patients with increasing histopathologic elements showed that most patients with cortical dysplasia had two to five (median: three) features of abnormal cortical development among these nine histopathologic elements. Furthermore, most patients with Palmini type I cortical dysplasia had two histopathologic elements (median: two), whereas patients with Palmini type II cortical dysplasia had a larger number of specific histological abnormalities (median: four).

For these reasons, useful selleck chemicals classification tree models and diagnostic models have been promptly built up by this technique in several medical realms such as cancer, autoimmune disease, haematological disease and mental diseases [16–19]. In our study, we used the data of a training set to construct a classification tree model that help accurately discriminate patients with active TB from patients with other respiratory diseases and healthy people, and then we applied this model to a test set to verify its performance of classification. Patients.  According to the case definitions described elsewhere, 75 patients

with active TB (active TB group) and 103 individuals (non-TB group) including 43 patients with common respiratory diseases (CRD subgroup) and 60 healthy controls (HC subgroup) were recruited from 309th hospital of Chinese PLA. These patients were randomly divided into two sets: a training set and a test set. Our study was approved by the ethics committee of Peking Union Medical College Hospital, and informed consent was obtained from each patient and volunteer. Case definitions.  Diagnosis GS-1101 in vivo of active TB was based on several criteria as follows: (1) sputum smear positive of

acid-fast bacilli or culture positive of M.tb, (2) positive TST, (3) specific symptoms such as persistent cough, weight loss, and night sweats and (4) characteristic changes of chest X-ray (CXR) like lung with cavities in upper lobes. Sputum smear-positive TB (SPP-TB) and smear-negative TB (SNP-TB) patients were classified according to widely accepted criteria [20], and all patients with SNP-TB were ultimately confirmed if their symptoms and CXR turned better after 3 months of anti-TB treatment. TST was performed on active TB group in their first visit according to standard intradermal

Mantoux test with 5 IU purified protein derivative of Bacillus Calmette-Guerin (BCG) (Chengdu institute of biological product, Sichuan, China) and read after 72 h. An induration of ≥5 mm is considered a positive test [21]. Anyone who met the criteria above or had a history of contact with active TB patients was excluded from the non-TB GBA3 group. To rule out latent patients with TB from this group, individuals that have received BCG vaccination before should be negative in IGRA (QuantiFERON®-TB Gold in Tube; Cellestis, Carnegie, Vic., Australia), which was performed according to the manufacturer’s instructions (cut-off value ≥ 0.35 IU/ml), and other individuals in the non-TB group should be negative of TST. In CRD subgroup, patients with lung cancer and sarcoidosis were diagnosed according to their biopsy evaluation, while patients with pneumonia, COPD, and bronchiectasia were diagnosed based on their clinical manifestations, radiographic features and prompt clinical response to regular therapy.

gingivalis Ixazomib [64]. Notably, P. gingivalis does not rely on immunological mechanisms for C5aR activation, since it can activate this complement receptor through C5a generated locally by its Arg-specific gingipains (HRgpA, RgpB) that have C5 convertase-like activity [64, 65]. Porphyromonas gingivalis also expresses a number of potent TLR2 ligands including serine lipids and lipoproteins [66, 67]. At the molecular level, the P. gingivalis-induced C5aR-TLR2 cross-talk in macrophages leads to synergistic activation of cAMP-dependent protein kinase A for inhibition of glycogen synthase kinase-3β and of iNOS-dependent

intracellular bacterial killing [64] (Fig. 3). In the murine periodontal tissue, C5aR signaling synergizes with TLR2 to induce secretion of cytokines that promote periodontal inflammation and bone loss (TNF, IL-1β, IL-6, and IL-17A). This is likely to enhance the fitness of P. gingivalis and other periodontitis-associated bacteria that require an inflammatory environment to secure critical nutrients, i.e. tissue breakdown products including peptides and hemin-derived iron. In stark contrast to the upregulation of bone-resorptive inflammatory cytokines, P. gingivalis-induced C5aR signaling in macrophages downregulates TLR2-induced https://www.selleckchem.com/products/Vorinostat-saha.html IL-12 and hence inhibits IFN-γ production and cell-mediated immunity against the bacteria [63, 65]. The selective inhibition

of

bioactive IL-12 (IL-12p35/IL-12p40) associated with C5aR-TLR2 cross-talk involves ERK1/2 signaling-dependent suppression of the IFN regulatory factor-1 (IRF-1), a transcription P-type ATPase factor that is crucial for the regulation of IL-12 p35 and p40 mRNA expression [65, 68]. Importantly, genetic ablation of C5aR or TLR2 promotes the killing of P. gingivalis in vivo [64, 69]. The inhibitory ERK1/2 pathway that regulates TLR2-induced IL-12 is also activated when P. gingivalis binds complement receptor 3 (CR3) on macrophages [70, 71] (Fig. 3). CR3 is a β2 integrin (CD11b/CD18) that can bind ligands when its high-affinity conformation is transactivated via inside-out signaling by other receptors such as chemokine receptors. Porphyromonas gingivalis induces TLR2-mediated transactivation of CR3 through an inside-out pathway that involves RAC1, PI3K, and cytohesin-1 [72, 73] (see Fig. 3). Upon binding CR3, P. gingivalis not only downregulates IL-12 but also enters macrophages in a relatively safe way [74], perhaps because CR3 is not linked to strong microbicidal mechanisms such as those activated by FcγR-mediated phagocytosis [75]. Indeed, P. gingivalis can persist intracellularly in WT macrophages for longer times than in CR3-deficient macrophages [74]. As alluded to above, P. gingivalis can activate C5aR signaling independently of the canonical activation of complement [64, 65]. In fact, P.

The DWT at an emptied bladder was 4.73 ± 0.97 mm at anterior wall, 3.83 ± 1.06 mm at posterior wall, 4.67 ± 1.12 mm at bladder base and 9.10 ± 2.11 mm at the bladder neck.87 When we measured the DWT of the same group of patients from

lower abdomen using an 8 MHz trans-abdominal sonographic probe (8C, GE, model LOGIQ P5/A5), the DWT was 0.926 ± 0.287 mm at a bladder volume of 250 mL, 0.739 ± 0.232 at the bladder capacity, and 0.925 ± 0.257 mm after the bladder capacity was corrected to 250 mL. Putting these data together, it is clear that DWT changes with bladder volume and varies greatly when measuring through different scanning route. Therefore, it is necessary to standardize the technique and scanning frequency in measurement of DWT if we try to compare NVP-LDE225 datasheet Roxadustat supplier DWT between different bladder disorder subgroups or performing a longitudinal study for DWT as biomarker of assessing OAB. The differences in the values of DWT obtained in various previous studies may have been caused by the use of different ultrasound probes with different frequency as well as to differences in the resolution of images. Review of previous reports found that studies using a higher frequency probe (7.5 MHz) reported a DWT of around 1–2 mm,80,81,83 whereas those using a low-frequency probe (2–5 MHz) reported a greater DWT of around 4–5 mm.77,82,88,89

In our previous studies, we used an 8 MHz high-frequency probe to measure the DWT either by TAU or TVU.85,86 Because the resolution power was able to differentiate the detrusor wall ZD1839 from the posterior rectus fascia, the measured DWT tended to be much less than would have been obtained using a 2–5 MHz low-frequency probe. Careful identification of the true bladder wall and accurate placement of cursors to measure the landmarks of DWT require experience. TVU assessment of mean BWT has been postulated to be a sensitive screening tool to detect DO in women with equivocal laboratory urodynamics. In women who have no evidence

of genuine SUI on laboratory studies, a cut-off of 6 mm of BWT by TVU has been highly suggested of having DO.89 Serati M et al. compared the ultrasound measurement of BWT in women with different urodynamic diagnosis and to correlate BWT to the different urodynamic findings of DO.90 They found that women with DO had a significantly higher BWT value. The measured BWT was 5.22 ± 1.17 mm in DO, 4.09 ± 0.86 mm in USI, 4.73 ± 1.27 mm in mixed incontinence, and 4.19 ± 1.14 mm in normal urodynamics. A cut-off of 6.5 mm for BWT had a positive predictive value of 100% for all DO. Although the ultrasound BWT showed a highly significant association with DO, data show a high level of overlap and it is only reliable in women with DO with a BWT cut-off value of >6.5 mm. The authors concluded that TVU-BWT cannot currently replace urodynamic testing.

Comparative studies in pigs have shown that porcine SP proteins influence sperm physiology.5 As such, HBPs play a major role during sperm transport33, FK866 cost while the heterodimer PSP-I/PSP-II maintains fertilizing capacity.40,74 This beneficial effect depends on the PSP-II moiety, active at doses as low as 0.75 mg/mL,39 concentrations present in the first spurts of the boar ejaculate. As listed elsewhere, porcine HBPs spermadhesins coat the sperm membrane during ejaculation, producing structural changes to the sperm plasma membrane

in relation to capacitation, ZP recognition and fertilization. AWN follows, for instance, the spermatozoa up to the ZP,34 perhaps because of their role in inhibiting

sperm capacitation,75,76 an effect that is lost when this protein is removed from the sperm surface.33 At the same time, such initial layer of proteins might provide an anchor for aggregated spermadhesins to further coat the sperm surface,77 further stabilizing the plasmalemma and preventing pre-mature acrosomal exocytosis. The heparin-binding AQN-3, the most prominent ZP-binding protein in boar spermatozoa, remains – for instance – attached to the sperm surface after capacitation (in vitro) and can only be recovered from the aggregating raft area of the apical ridge of the sperm head.78,79 The non-heparin-binding protein PSP-I prevents pre-mature capacitation and acrosome exocytosis.80 selleck kinase inhibitor Whether these proteins are also involved in the interaction

between spermatozoa and oviductal epithelium during sperm capacitation remains to be explored. Increasing evidence exist that SP proteins are able to interact with the vaginal, cervical and, particularly, the uterine epithelium to elicit a series of changes in the immune responsiveness of the female, apparently modulated by pro- and anti-inflammatory SP proteins.81 This is not surprising, because the ejaculate (spermatozoa mafosfamide and SP) is to be considered foreign by the female and thus prompt to rejection. Deposition of semen into the vagina or the uterine cavity elicits a massive invasion of PMNs towards the lumen, followed by the formation of neutrophil extracellular traps (NETs) and sperm phagocytosis. Although PMN presence and infiltration are oestrogen-dependent,82 PMN migration to the surface epithelium and lumen can be elicited by SP glycoproteins (spermadhesins7) and pro-inflammatory-soluble cytokines83 (Fig. 2). This primary inflammatory reaction cleanses the intrauterine lumen from foreign cells, proteins and eventual pathogens, in preparation for the descending embryo. On the other hand, it does not occur in the oviduct, where spermatozoa find a haven until fertilization.8,9,27 Induction of PMN invasion is, evidently, not the only effect of the SP on the female.

The antigen-specific responses among individuals infected with L. braziliensis also

revealed a significant expansion of T cells expressing Vβ12 (Fig. 3). Interestingly, this was the same subpopulation identified by Clarencio et al. in CL caused by L. braziliensis and stimulated by SLA of L. amazonensis[29]. This finding may suggest an existence of common dominant response between different species of Leishmania leading to the expansion of a similar subpopulation of T cells. Frequency differences are only one possible measure of selleck chemicals the involvement of a specific subpopulation of T cells in an active immune response. It is possible that slight changes or no global change in the frequency of T cell subpopulations will be noted due to a balance between expansion and death of responding T cells. However, by determining the portion of a given subpopulation committed to an activated phenotype, memory phenotype or producing specific cytokines, we can determine

their relative involvement and possible functional role in a protective or pathogenic immune response. Thus, we performed comparative analyses between the different Vβ subpopulations of the proportion of cells expressing either a marker of late T cell activation, the class II molecule, HLA-DR, or a marker associated with many memory T cells, CD45RO. These markers were measured without in vitro antigenic restimulation with the goal of determining their involvement in the host actively infected with Leishmania. Strikingly, CD4+ T cells expressing Vβ find more regions 5·2, 11 and 24 displayed a significantly higher portion of cells expressing CD45RO and HLA-DR (Fig. 4). Thus, these subpopulations demonstrated a phenotype consistent with greater involvement in an ongoing immune response

than the tuclazepam other T cell subpopulations. Importantly, two of these subpopulations (Vβ5·2 and Vβ11 CD4+ T cells) also displayed an expansion after antigen specific stimulation in vitro (Fig. 3). In order to understand more clearly the functional potential of specific subpopulations of CD4+ T cells based on Vβ expression, we went on to measure their relative commitment to production of antigen-specific proinflammatory (IFN-γ and TNF-α) and anti-inflammatory (IL-10) cytokines. Strikingly, the same three Vβ-expressing subpopulations arose as having a disproportionately high percentage of the SLA-stimulated T cells committed to cytokine production compared to the majority of the other Vβ-expressing T cell populations (Fig. 5). Thus, CD4+ T cell subpopulations defined by Vβ 5·2, 11 and 24 in CL patients displayed higher production of IFN-γ, TNF-α and IL-10 compared to several other subpopulations of T cells in CL patients. An important aspect of human leishmaniasis and other infectious diseases is the balance of inflammatory and down-regulatory cytokines.

5A). Following resting, TCR stimulation can induce phosphorylation of Akt at S473 and Foxo1a at S256 in WT T cells. Such phosphorylation was decreased in TSC1KO thymocytes and peripheral T cells (Fig. 5B).

However, TCR-induced Akt phophorylation at T308 was similar between WT and TSC1KO T cells (data not shown). Thus, while mTORC1 signaling is enhanced, mTORC2 signaling and Akt activities are impaired in TSC1-deficient T cells. Akt is activated by phosphorylation at T308 and S473 by PI3K/PDK1 and mTORC2 respectively 29, 31, 32. To determine if the decreased Akt activity observed in TSC1KO T cells may contribute to the increased death subsequent to TCR stimulation, check details we transduced these cells with retrovirus expressing either the constitutively active (ca) form of Akt (Akt-DD) or Akt-S374D mutant. Death of the GFP+ Akt-DD-expressing TSC1KO T cells was significantly reduced in comparison to the MigR1-GFP+ vector control cells in both CD4+ and CD8+ T-cell subsets after TCR stimulation (Fig. 5C). However, Akt-S473D manifested minimal effects in preventing death of TSC1KO T cells. Thus, although enhanced Akt activity can promote TSC1KO T-cell survival,

relief of the requirement of mTORC2-mediated Akt activation is not sufficient to rescue TSC1KO T cells from death, suggesting complex regulation of T-cell survival by Kinase Inhibitor Library purchase TSC1. CD28 co-stimulatory receptor promotes PI3K/Akt activation during T-cell activation. Stimulation of TSC1KO CD4+ T cells through the TCR and CD28 reduced TSC1KO CD4+ T-cell death, correlated with decreased ROS production, and improved mitochondrial integrity as compared with stimulation by TCR

Sodium butyrate alone. However, the protective effect of CD28 was not observed in TSC1KO CD8+ T cells (Fig. 5D). In addition, CD28 co-stimulation was not able to restore Akt phosphorylation at S473 in TSC1KO T cells (Fig. 5E), suggesting that CD28 promotes TSC1KO T-cell survival through an mTORC2-independent mechanism. We further asked whether the increase in ROS production may contribute to the death of TSC1KO T cells. Treatment with N-acetylcysteine (NAC), a ROS scavenger, resulted in decreased death of TSC1KO CD4+ T cells, but not CD8+ T cells, suggesting that increased ROS production contributes to increased death of TSC1KO CD4+ T cells. Inhibition of mTOR activity has been reported to enhance survival and reduce contraction of viral specific CD8+ T cells 10. However, rapamycin treatment could not prevent increased ROS production, restore mitochondrial membrane integrity, or rescue the cells from death. In fact, it made TSC1KO T cells more prone to death (Fig. 5D). Similarly, rapamycin treatment could not restore early activation of TSC1KO T cells, although CD28 co-stimulation can slightly increase CD25 and CD69 expression (Fig. 5F).

Moreover, memory B cells have been detected early in the immune response, prior to the peak of the GC reaction [21, 23, 34, 36], suggesting that memory B cells emerge early from the GC or, alternatively, independently of GCs. To assess the relative contribution of GC-dependent and GC-independent pathways to memory B cell formation, an antigen-based cell-enrichment strategy was developed [20, 21]. Immunizing mice with the soluble protein phycoerythrin (PE), a fluorescent Td antigen, made

it possible to track PE-binding B cells in order to study memory and GC B cells. In this way, a precursor cell population was identified that could give rise to GC B cells and later differentiate into memory B or plasma cells. Early in the response and independently of the GC reaction, FDA approved Drug Library manufacturer these precursors could differentiate

directly into memory B cells. The GC-independent memory B cells mainly retained IgM expression and were less mutated compared with the GC-derived memory B cells. In another model [23], conditional ablation learn more of Bcl-6, a transcription factor pivotal for the survival of GC B cells [39], was used to investigate the GC-dependent and GC-independent pathways in response to the Td antigen, NP-CGG, using IgG1+ NP-specific B cells as read-out [23]. Deletion of Bcl-6 in B cells did not affect B cell development per se whereas it did reduce the number of antigen-specific GC B cells after MYO10 immunization. However, antigen-specific memory B cells were still present, indicating that memory B cells develop

independently of GCs. There seems to be a difference although between memory B cells that develop in a GC-independent compared with GC-dependent manner with respect to SHM. Those that developed in a GC-independent manner did not show signs of SHM by contrast to the GC-dependent memory B cells. Early in the primary response, the GC-independent unmutated memory B cells undergo expansion to become long-lived cells that express antibodies with low affinity. As the response progresses, these cells become resting and are later joined by mutated GC progenies. Together these two populations comprise the memory B cell pool at comparable frequencies and mediate secondary antibody responses upon adoptive transfer. Moreover, and consistent with memory B cells expressing CD80, PDL-2 and CD73 [15], these markers were also detected on memory B cells in this study although not analysed in detail. Finally, it was suggested that the memory compartment is generated as two layers of cells: those uniquely tailored to the pathogen and those that are unmutated in order to accommodate cross-reacting specificities of related pathogens. TFH cells have been suggested as an essential cellular component for GC formation [5-8], and Bcl-6 is pivotal also for the differentiation of TFH cells [5]. In the study just discussed [23], Bcl-6 was conditionally deleted selectively in CD4-expressing cells.