An Overview of B-1 Cells as Antigen-Presenting Cells

The role of B cells as antigen-presenting cells (APCs) has been extensively studied, mainly in relation to the activation of memory T cells. Considering the B cell subtypes, the role of B-1 cells as APCs is beginning to be explored. Initially, it was described that B-1 cells are activated preferentially by T-independent antigens. However, some reports demonstrated that these cells are also involved in a T-dependent response. The aim of this review is to summarize information about the ability of B-1 cells to play a role as APCs and to briefly discuss the role of the BCR and toll-like receptor signals in this process. Furthermore, some characteristics of B-1 cells, such as natural IgM production and phagocytic ability, could interfere in the participation of these cells in the onset of an adaptive response.FAPESPUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Sao Paulo, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Sao Paulo, BrazilFAPESP: 2008/58561-0FAPESP: 2015/01986-2Web of Scienc

Could a B-1 Cell Derived Phagocyte “Be One” of the Peritoneal Macrophages during LPS-Driven Inflammation?

The inflammatory response is driven by signals that recruit and elicit immune cells to areas of tissue damage or infection. The concept of a mononuclear phagocyte system postulates that monocytes circulating in the bloodstream are recruited to inflamed tissues where they give rise to macrophages. A recent publication demonstrated that the large increase in the macrophages observed during infection was the result of the multiplication of these cells rather than the recruitment of blood monocytes. We demonstrated previously that B-1 cells undergo differentiation to acquire a mononuclear phagocyte phenotype in vitro (B-1CDP), and we propose that B-1 cells could be an alternative origin for peritoneal macrophages. A number of recent studies that describe the phagocytic and microbicidal activity of B-1 cells in vitro and in vivo support this hypothesis. Based on these findings, we further investigated the differentiation of B-1 cells into phagocytes in vivo in response to LPS-induced inflammation. Therefore, we investigated the role of B-1 cells in the composition of the peritoneal macrophage population after LPS stimulation using osteopetrotic mice, BALB/Xid mice and the depletion of monocytes/macrophages by clodronate treatment. We show that peritoneal macrophages appear in op/op(−/−) mice after LPS stimulation and exhibit the same Ig gene rearrangement (VH11) that is often found in B-1 cells. These results strongly suggest that op/op(−/−) peritoneal “macrophages” are B-1CDP. Similarly, the LPS-induced increase in the macrophage population was observed even following monocyte/macrophage depletion by clodronate. After monocyte/macrophage depletion by clodronate, LPS-elicited macrophages were observed in BALB/Xid mice only following the transfer of B-1 cells. Based on these data, we confirmed that B-1 cell differentiation into phagocytes also occurs in vivo. In conclusion, the results strongly suggest that B-1 cell derived phagocytes are a component of the LPS-elicited peritoneal macrophage population

Identificação de cepas de Escherichia coli enteropatogênicas em amostras de fezes, por reação de imunofluorescência direta

A study of 121 patients with acute diarrhea was made at the Pediatric Clinic of the Santa Casa de S. Paulo (the S. Paulo Charity Hospital). Etiological diagnosis of 121 cases was carried out through the classical bacteriological method and direct fluorescent antibody tests for the identification of E. coli. The antibiotic sensitivity of these bacteria to different antimicrobials was determined by the Minimum Inhibitory Concentration (MIC) method. Fifty-six positive cases were found; 89.3% of which corresponded to different serotypes of enter o pathogenic E. coli (89.3%), when the direct fluorescent antibody test was used. The classic bacteriological method bared four Salmonella strains and two Shigella. The MIC showed the E. coli to be more sensitive to Gentamicin and Amikacin than to other antibiotics.Foi realizado diagnóstico etiológico de casos de diarréia aguda em 121 pacientes internados na Clínica Pediátrica do Hospital da Santa Casa de São Paulo, Brasil. Foram utilizados os métodos bacteriológico clássico e de reação de imunofluorescência direta para a identificação de cepas de Escherichia coli enteropatogênicas: para estudo da sensibilidade das cepas de Escherichia coli isoladas, a diferentes antibióticos, foi usado o método de Concentração Inibitória Minima (CIM). Dos 56 casos positivos, 89,3% correspondiam a diferentes sorotipos enteropatogênicos de Escherichia coli, quando utilizada a técnica de imunofluorescência direta. O método bacteriológico clássico revelou ainda, nos 121 casos examinados, 4 cepas de Salmonella e 2 de Shigella. No estudo da CIM verificou-se maior sensibilidade das cepas de Escherichia coli enteropatogênicas estudadas à Gentamicina e Amikacina, do que aos outros antibióticos

Evaluation of lymphocyte levels in a random sample of 218 elderly individuals from São Paulo city

BACKGROUND: Age-associated changes in the immune system cause decreased protection after vaccination and increased rates of infections and tumor development. METHODS: Lymphocyte percentages were compared by gender and age to establish differences between subtypes. Three mL blood samples were obtained from 218 randomly selected individuals (60-101 years old) who live in São Paulo city. Blood was lysed with Tris phosphate buffer and stained for 30 minutes with monoclonal antibodies (CD3PerCP, CD4FITC, CD8Pe, CD19Pe) for analysis by flow cytometry. Statistical analysis was by ANOVA. RESULTS: The percentage of CD4+ T cells (p-value = 0.005) and the CD4/CD8 ratio (p-value = 0.010) were lower in men, whereas the percentage of CD8+ T cells was lower (p-value = 0.002) in women; the percentage of B cells (CD19+ ) was similar between groups. Individuals grouped by gender and age range and compared showed a drop in CD4+ cells in 75 to 79-year-old men (female: 46.1% ± 8.1% and male: 38.8% ± 10.5%; p-value = 0.023). Also, the 80 to 84-year-old group of men had a higher percentage of CD8+ (female: 20.8% ± 8.2%, and male: 27.2% ± 8.2%; p-value = 0.032). Low percentages of B cells were detected in men in the 75 to 79-year-old (p-value = 0.003), 85 to 89-year-old (p-value = 0.020) and older than 90 year old (p-value = 0.002) age ranges. CONCLUSION: Elderly men present with more changes in lymphocyte subsets compared to elderly women. These findings could demonstrate impairment in the immune response since the lower CD4+ in men would provide less help to B cells (also lower in men) in terms of antibody production. In addition, the increase in CD8+ cells in this group could represent chronic inflammation observed during the aging process.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Immunology DepartmentUniversidade de São Paulo Faculdade de Medicina de Ribeirão PretoUniversidade de São Paulo Escola de Saúde PúblicaUniversidade Federal de São Paulo (UNIFESP) Biosciences DepartmentUNIFESP, Immunology DepartmentUNIFESP, Biosciences DepartmentSciEL

Mechanism of photoluminescence in intrinsically disordered CaZrO3 crystals: First principles modeling of the excited electronic states

CaZrO3 (CZO) powders obtained by the polymeric precursor method at 400 °C, and then, the samples were annealed at different temperatures (400, 600, 800, and 1000 °C) and characterized by X-ray diffraction, Raman and ultraviolet–visible spectroscopic methods, along with photoluminescence (PL) emissions. First principle calculations based on the density functional theory (DFT), using a periodic cell models, provide a theoretical framework for understanding the PL spectra based on the localization and characterization of the ground and electronic excited states. Fundamental (singlet, s) and excited (singlet, s*, and triplet, t*) electronic states were localized and characterized using the ideal and distorted structures of CZO. Their corresponding geometries, electronic structures, and vibrational frequencies were obtained. A relationship between the different morphologies and structural behavior has also been established. Polarized structures were identified by the redistribution of the 4dz2, 4dyz, and 4dxy (Zr) orbitals at the conduction band and the 2pz (O) orbital in the valence band for s, s* and t*. Analysis of the vibrational eigenvector modes of these electronic states reveals a relationship between them via asymmetric bending and stretching modes that arise from Zr atom displacements due to polyhedral [ZrO6] distortion. Furthermore, the results provided an insight into the PL emissions of the as-synthesized CaZrO3 and led to the conclusion that the presence of electronically excited states is strongly related to the structural order-disorder effects (polyhedral distortion) at short range for both [ZrO6] and [CaO8] clusters

Experimental and theoretical study of the energetic, morphological, and photoluminescence properties of CaZrO3:Eu3+

In this study, we present a combined experimental and theoretical study of the geometry, electronic structure, morphology, and photoluminescence properties of CaZrO3:Eu3+ materials. The polymeric precursor method was employed to synthesize CaZrO3:Eu3+ crystals, while density functional theory calculations were performed to determine the geometrical and electronic properties of CaZrO3:Eu3+ in its ground and excited electronic states (singlet and triplet). The results were combined with X-ray diffraction (XRD) measurements to elucidate the local structural changes induced by the introduction of Eu3+ in the crystal lattice. This process results in the formation of intermediate levels in the band-gap (Egap) region, narrowing its width. The PL emissions were rationalized by characterizing the electronic structure of the excited singlet and triplet electronic states, which provided deep insight into the main structural and electronic fingerprints associated with [CaO8], [EuO8], and [ZrO6] clusters. In addition, the Wulff construction, obtained from the first-principles calculations, was used to clarify the experimental morphologies. These results extend our fundamental understanding of the atomic processes that underpin the Eu doping of CaZrO3

Improvement of Mesenchymal Stem Cell Immunomodulatory Properties by Heat-Killed Propionibacterium acnes via TLR2

Mesenchymal stem cells (MSCs) are an essential tool for regenerative medicine, which aims to develop new technologies to improve their effects to obtain useful transplantation results. MSC immunomodulatory role has been just demonstrated; however, how they react when they are stimulated by an adjuvant is poorly understood. Our group showed the adjuvant effect of killed Propionibacterium acnes (P. acnes) on hematopoietic stem cells. As these cells share the same MSCs bone marrow (BM) site and interact with each other, here we evaluated the P. acnes and its soluble polysaccharide (PS) effect on MSCs and their immunomodulatory role in a murine model of traumatic brain injury (TBI). The bacteria increased the absolute number of MSCs, including MSC subpopulations, and maintained MSC plasticity. P. acnes and PS enhanced MSC proliferation and improved their immunomodulatory effect. P. acnes-MSC and PS-MSC transplantation increased anti-inflammatory cytokine expression and diminished pro-inflammatory cytokine expression after injury. This effect seemed to be mediated via TLR2 since P. acnes-KOTLR2-MSC transplantation decreased TGF-β and IL-10 expression. Increasing in neural stem cells and neuroblasts after PS-MSC transplantation was also observed. The adjuvant effect of P. acnes is an alternative means of expanding MSCs and important to identify their subpopulations to know better their role under exogenous stimuli including inflammation resolution in an experimental model

Role of B lymphocytes in the infarcted mass in patients with acute myocardial infarction

Despite early reperfusion, patients with ST segment elevation myocardial infarction (STEMI) may present large myocardial necrosis and significant impairment of ventricular function. The present study aimed to evaluate the role of subtypes of B lymphocytes and related cytokines in the infarcted mass and left ventricular ejection fraction obtained by cardiac magnetic resonance imaging performed after 30 days of STEMI. This prospective study included 120 subjects with STEMI submitted to pharmacoinvasive strategy. Blood samples were collected in subjects in the first (D1) and 30th (D30) days post STEMI. The amount of CD11b+ B1 lymphocytes (cells/ml) at D1 were related to the infarcted mass (rho = 0.43; P=0.033), measured by cardiac MRI at D30. These B1 cells were associated with CD4+ T lymphocytes at D1 and D30, while B2 classic lymphocytes at day 30 were related to left ventricular ejection fraction (LVEF). Higher titers of circulating IL-4 and IL-10 were observed at D30 versus D1 (P=0.013 and P<0.001, respectively). Titers of IL-6 at D1 were associated with infarcted mass (rho = 0.41, P<0.001) and inversely related to LVEF (rho = -0.38, P<0.001). After multiple linear regression analysis, high-sensitivity troponin T and IL-6 collected at day 1 were independent predictors of infarcted mass and, at day 30, only HDL-C. Regarding LVEF, high-sensitivity troponin T and high-sensitivity C-reactive protein were independent predictors at day 1, and B2 classic lymphocytes, at day 30. In subjects with STEMI, despite early reperfusion, the amount of infarcted mass and ventricular performance were related to inflammatory responses triggered by circulating B lymphocytes