Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2018-05-22T13:24:04Z No. of bitstreams: 1 PDF - Gleydson Kleyton Moura Nery.pdf: 28016541 bytes, checksum: dee318975b7418cd78bfb23b8b8cb2ec (MD5) / Approved for entry into archive by Secta BC (secta.csu.bc@uepb.edu.br) on 2018-05-23T16:37:33Z (GMT) No. of bitstreams: 1 PDF - Gleydson Kleyton Moura Nery.pdf: 28016541 bytes, checksum: dee318975b7418cd78bfb23b8b8cb2ec (MD5) / Made available in DSpace on 2018-05-23T16:37:33Z (GMT). No. of bitstreams: 1 PDF - Gleydson Kleyton Moura Nery.pdf: 28016541 bytes, checksum: dee318975b7418cd78bfb23b8b8cb2ec (MD5) Previous issue date: 2017-07-04 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The present study aims to adapt and apply a Biotic Integrity Index (IBI) for reservoirs in the Paraíba River basin located without Brazilian semiarid, with the use of fish community sites as a subsidy. For that, 20 points were sampled in 5 reservoirs with four sample stations from July 2016 to March 2017. The IBI was obtained by elaboration and selection of metrics based on the community studied. The study was divided into two chapters. In the first one, the factors that explain the adaptive success of Oreochromis niloticus in the aquatic systems of the semiarid were oriented. It was found that the invasion ability of O. niloticus was associated with both environmental factors and biological interactions. However, there is a strong influence of environmental variables linked to these relationships, since a dissimilarity of systems regarding water quality and habitat structuring directly influence the structuring of the community in terms of composition as trophic relationships. In the second chapter, the biotic integrity index based on the fish community was proposed and applied as an environmental assessment tool for non - semiarid systems. The composition of the index was based on the metrics% native species,% endemic species,% invasive species, abundance of cichlids, abundance of species,% sp. piscivorous and% sp. intolerant An application of the index for the semiarid to the problem, the limnological state of the environment, such as total phosphorus (r² = -0.62, p <0.005), chlorophyll a (r² = -0.74, p < 05) and volume (r² = 0.33, p <0.005). The study points to a community of fish as a good indicator of environmental quality, since, during the studied period, it reduced the quality of the quality of the environment with the direct reflection in the fish community. / O presente estudo tem como objetivo adaptar e aplicar um Índice de Integridade Biótica (IBI), para reservatórios da bacia do rio Paraíba localizado no semiárido brasileiro, tendo como subsídio a utilização de atributos da comunidade de peixes. Para tanto, foram amostrados 20 pontos distribuídos em 5 reservatórios com quatros estações amostrais no período de julho/2016 a março/2017. O IBI foi obtido pela elaboração e seleção de métricas com base na comunidade estudada. O estudo foi dividido em dois capítulos. No primeiro, foram avaliados os fatores que explicam o sucesso adaptativo de Oreochromis niloticus nos sistemas aquáticos do semiárido. Constatou-se que a habilidade de invasão de O. niloticus foi associada tanto a fatores ambientais, quanto as interações biológicas. Contudo, há uma forte influência das variáveis ambientais atrelados a estas relações, uma vez que, a dissimilaridade dos sistemas quanto a qualidade de água (eutrofização) e estruturação do habitat influenciam diretamente na estruturação da comunidade quanto a composição e as relações tróficas. No segundo capítulo, foi proposto e aplicado o índice de integridade biótica com base na comunidade de peixes, como ferramenta de avaliação ambiental de sistemas no semiárido. A composição do índice se baseou nas métricas % espécies nativas, % espécies endêmicas, % espécies invasoras, abundância de ciclídios, abundância de characiformes, % sp. piscívoros e % sp. intolerantes. A aplicação do índice para o semiárido foi eficaz, apresentando correlações significativas com variáveis que descriminam o status limnológico do ambiente, tais como, fosforo total (r²= -0,62; p< 0,005), clorofila-a (r²= -0,74; p< 0,05) e volume (r²= 0,33; p< 0,005). O estudo aponta a comunidade de peixes como um bom indicador de qualidade ambiental, uma vez que, ao longo do período estudado houve redução da qualidade cênica do ambiente com reflexo direto na comunidade de peixes.

Introduction: Bivalirudin and heparin are the two most commonly used anticoagulants used during Percutaneous Coronary Intervention (PCI). The results of Randomized Controlled Trials (RCTs) comparing bivalirudin versus heparin monotherapy in the era of radial access are controversial, questioning the positive impact of bivalirudin on bleeding. The purpose of this systematic review is to summarize the results of RCTs comparing the efficacy and safety of bivalirudin versus heparin with or without Glycoprotein IIb/IIIa Inhibitors (GPI). Methods: This systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA statements for reporting systematic reviews. We searched the National Library of Medicine PubMed, Clinicaltrial.gov and the Cochrane Central Register of Controlled Trials to include clinical studies comparing bivalirudin with heparin in patients undergoing PCI. Sixteen studies met inclusion criteria and were reviewed for the summary. Findings: Several RCTs and meta-analyses have demonstrated the superiority of bivalirudin over heparin plus routine GPI use in terms of preventing bleeding complications but at the expense of increased risk of ischemic complications such as stent thrombosis. The hypothesis of post-PCI bivalirudin infusion to mitigate the risk of acute stent thrombosis has been tested in various RCTs with conflicting results. In comparison, heparin offers the advantage of having a reversible agent, of lower cost and reduced incidence of ischemic complications. Conclusion: Bivalirudin demonstrates its superiority over heparin plus GPI with better clinical outcomes in terms of less bleeding complications, thus making it as anticoagulation of choice particularly in patients at high risk of bleeding. Further studies are warranted for head to head comparison of bivalirudin to heparin monotherapy to establish an optimal heparin dosing regimen and post-PCI bivalirudin infusion to affirm its beneficial effect in reducing acute stent thrombosis.

In the first part of this thesis, we investigate a way to find the complex structure moduli, for a given background of type IIB string theory in the presence of flux in special cases. We introduce a way to compute the complex structure and axion dilaton moduli explicitly. In the second part, we discuss $(0,2)$ supersymmetric versions of some recent exotic $mathcal{N}=(2,2)$ supersymmetric gauged linear sigma models, describing intersections of Grassmannians. In the next part, we consider mirror symmetry for certain gauge theories with gauge groups $F_4$, $E_6$, and $E_7$. In the last part of this thesis, we study whether certain branched-double-cover constructions in Landau-Ginzburg models can be extended to higher covers. / Doctor of Philosophy / This thesis concerns string theory, a proposal for unification of general relativity and quantum field theory. In string theory, the building block of all the particles are strings, such that different vibrations of them generate particles. String theory predicts that spacetime is 10-dimensional. In string theorist's intuition, the extra six-dimensional internal space is so small that we haven't detected it yet. The physics that string theory predicts we should observe, is governed by the shape of this six-dimensional space called a `compactification manifold.' In particular, the possible ways in which this geometry can be deformed give rise to light degrees of freedom in the associated observable physical theory. In the first part of this thesis, we determine these degrees of freedom, called moduli, for a large class of solutions of the so-called type IIB string theory. In the second part, we focus on constructing such spaces explicitly. We also show that there can be different equivalent ways of constructing the same internal space. The third part of the thesis concerns mirror symmetry. Two compactification manifolds are called mirror to each other, when they both give the same four-dimensional effective theory. In this part, we describe the mirror of two-dimensional gauge theories with $F_4$, $E_6$, and $E_7$ gauge group, using the Gu-Sharpe proposal.

O fósforo é um dos minerais mais abundantes no corpo além de ser essencial para muitos processos biológicos. A homeostase do fósforo depende da absorção no intestino, da excreção renal, da remodelação óssea e de hormônios como o paratormônio, calcitriol e FGF-23. Nos pacientes com doença renal crônica, a excreção urinária de fósforo está comprometida levando à hiperfosfatemia, que contribui para o aumento da morbidade e mortalidade desses pacientes. A absorção intestinal de fósforo no intestino delgado, particularmente via cotransportadores NaP-IIb e PiT-1, é pouco estudada. O objetivo desse estudo foi avaliar os efeitos de dietas com diferentes concentrações de fósforo na expressão proteica e gênica dos cotransportadores NaP-IIb e PiT-1, bem como na apoptose dos enterócitos dos diferentes segmentos do intestino delgado de animais controles e urêmicos. Estudamos setenta e seis ratos Wistar machos, inicialmente divididos em dois grupos: controles (C) e urêmicos (Nx). Cada grupo foi subdividido em outros três, de acordo com a concentração de fósforo (P) na dieta: dieta Baixa (0,2%), dieta Padrão (0,54%) e dieta Alta (0,9%). Analisamos parâmetros bioquímicos (creatinina, P, Cai, PTH e FGF-23), a expressão proteica dos cotransportadores, através de Western Blotting, ELISA e imunofluorescência, a expressão gênica por PCR em tempo real e a apoptose dos enterócitos pela técnica TUNEL. Os resultados mostraram que os níveis séricos de creatinina, P, PTH e FGF-23 foram significativamente mais elevados nos animais Nx. Nos animais C com dieta baixa em P observamos aumento da expressão proteica do cotransportador NaP-IIb em todos os segmentos do intestino enquanto, no Nx Baixo, a expressão desse cotransportador foi menor somente no jejuno. Quanto ao PiT-1, sua expressão foi menor no íleo do grupo Nx Alto comparado ao seu respectivo controle. A expressão gênica do cotransportador NaP-IIb foi menor no jejuno do Nx Alto e maior no íleo desse mesmo grupo em relação aos seus respectivos controles. A expressão gênica do PiT-1 foi maior em todos os segmentos do grupo Nx Baixo em relação aos seus controles. Detectamos uma correlação direta entre a expressão gênica do NaP-IIb no jejuno com o fósforo sérico. A expressão gênica do PiT-1 no jejuno correlacionou-se com o fósforo sérico e no duodeno e jejuno, com os níveis séricos de FGF-23. No duodeno e no jejuno, a porcentagem de enterócitos apoptóticos foi maior nos animais Nx Alto comparados aos controles, particularmente no duodeno a porcentagem dessas células também foi maior no grupo Nx Baixo e controle padrão. Já no jejuno, tanto o grupo Nx baixo quanto no Nx Padrão observamos menos células apoptóticas que nos seus respectivos controles. Quando analisamos conjuntamente todos os segmentos intestinais o grupo Nx alto apresentou mais células apoptóticas que o controle e o oposto foi observado nos grupos Nx Baixo e Nx Padrão. Em conclusão, dietas com distintas concentrações de fósforo promovem modificações na expressão proteica e gênica dos cotransportadores NaP-IIb e PiT-1 no intestino delgado que não seguem um padrão uniforme. A sobrecarga de fósforo aumenta a porcentagem de enterócitos apoptóticos nos animais urêmicos / Phosphorus is one of the most abundant minerals in the body besides being essential for many biological processes. Phosphorus homeostasis depends on absorption in the small intestine, renal excretion, bone remodeling and hormones such as parathyroid hormone, calcitriol and FGF-23. In patients with chronic kidney disease phosphorus urinary excretion is compromised leading to hyperphosphatemia, which contributes to increased morbidity and mortality of these patients. Intestinal absorption of phosphorus in the small intestine, particularly of NaP-IIb and PiT-1 cotransporters is poorly studied. The aim of this study was to evaluate the effects of diets with different concentrations of phosphorus in protein expression and gene of NaP-IIb and PiT-1 cotransporters as well as in apoptosis of enterocytes of different segments of intestine in control and uremic animals. We studied seventy-six male Wistar rats initially divided into two groups: controls (C) and uremic (Nx). Each group was subdivided into three others, according to the phosphorus concentration in the diet: Low diet (0.2% P), Standard diet (0.54% P) and High diet (0.9% P). We analyzed biochemical parameters (creatinine, P, iCa, PTH and FGF-23), protein expression of cotransporters, using Western Blot, ELISA, immunofluorescence, real-time PCR and apoptosis of enterocytes using the TUNEL technique. Results showed that serum creatinine, P, PTH and FGF-23 were significantly higher in Nx animals. In C animals with a diet low in P we observed increase in protein expression of NaP-IIb cotransporter in all segments of the intestine while in low Nx expression of this cotransporter was lower only in jejunum. As for PiT-1 expression was lower in the ileum of the high Nx group compared to their respective control. Gene expression of NaP-IIb cotransporter was lower in the jejunum of high Nx and higher in the ileum of the same group as compared to their respective controls. PiT-1 gene expression was higher in all segments of the low Nx group compared to their controls. We detected a direct correlation between the gene expression of NaP-IIb in jejunum and serum phosphorus. Gene expression of PiT-1 correlated with serum phosphorus in the jejunum, and correlated with the serum levels of FGF-23 in the jejunum and duodenum. In the duodenum and jejunum the percentage of apoptotic enterocytes was higher in high Nx animals compared to controls; particularly in the duodenum the percentage of these cells was also higher in low Nx group and standard control. In the jejunum in both low Nx group and standard Nx we observed fewer apoptotic cells than in their respective controls. When we analyze all intestinal segments together the high Nx group had more apoptotic cells than the control, and the opposite was observed in the low Nx group and standard Nx group. In conclusion, diets with different phosphorus concentrations promote changes in protein expression and gene of NaP-IIb and PiT-1 cotransporters in the small intestine that do not follow a uniform pattern. Phosphorus overhead increases the percentage of apoptotic enterocytes in uremic animals

O fósforo é um dos minerais mais abundantes no corpo além de ser essencial para muitos processos biológicos. A homeostase do fósforo depende da absorção no intestino, da excreção renal, da remodelação óssea e de hormônios como o paratormônio, calcitriol e FGF-23. Nos pacientes com doença renal crônica, a excreção urinária de fósforo está comprometida levando à hiperfosfatemia, que contribui para o aumento da morbidade e mortalidade desses pacientes. A absorção intestinal de fósforo no intestino delgado, particularmente via cotransportadores NaP-IIb e PiT-1, é pouco estudada. O objetivo desse estudo foi avaliar os efeitos de dietas com diferentes concentrações de fósforo na expressão proteica e gênica dos cotransportadores NaP-IIb e PiT-1, bem como na apoptose dos enterócitos dos diferentes segmentos do intestino delgado de animais controles e urêmicos. Estudamos setenta e seis ratos Wistar machos, inicialmente divididos em dois grupos: controles (C) e urêmicos (Nx). Cada grupo foi subdividido em outros três, de acordo com a concentração de fósforo (P) na dieta: dieta Baixa (0,2%), dieta Padrão (0,54%) e dieta Alta (0,9%). Analisamos parâmetros bioquímicos (creatinina, P, Cai, PTH e FGF-23), a expressão proteica dos cotransportadores, através de Western Blotting, ELISA e imunofluorescência, a expressão gênica por PCR em tempo real e a apoptose dos enterócitos pela técnica TUNEL. Os resultados mostraram que os níveis séricos de creatinina, P, PTH e FGF-23 foram significativamente mais elevados nos animais Nx. Nos animais C com dieta baixa em P observamos aumento da expressão proteica do cotransportador NaP-IIb em todos os segmentos do intestino enquanto, no Nx Baixo, a expressão desse cotransportador foi menor somente no jejuno. Quanto ao PiT-1, sua expressão foi menor no íleo do grupo Nx Alto comparado ao seu respectivo controle. A expressão gênica do cotransportador NaP-IIb foi menor no jejuno do Nx Alto e maior no íleo desse mesmo grupo em relação aos seus respectivos controles. A expressão gênica do PiT-1 foi maior em todos os segmentos do grupo Nx Baixo em relação aos seus controles. Detectamos uma correlação direta entre a expressão gênica do NaP-IIb no jejuno com o fósforo sérico. A expressão gênica do PiT-1 no jejuno correlacionou-se com o fósforo sérico e no duodeno e jejuno, com os níveis séricos de FGF-23. No duodeno e no jejuno, a porcentagem de enterócitos apoptóticos foi maior nos animais Nx Alto comparados aos controles, particularmente no duodeno a porcentagem dessas células também foi maior no grupo Nx Baixo e controle padrão. Já no jejuno, tanto o grupo Nx baixo quanto no Nx Padrão observamos menos células apoptóticas que nos seus respectivos controles. Quando analisamos conjuntamente todos os segmentos intestinais o grupo Nx alto apresentou mais células apoptóticas que o controle e o oposto foi observado nos grupos Nx Baixo e Nx Padrão. Em conclusão, dietas com distintas concentrações de fósforo promovem modificações na expressão proteica e gênica dos cotransportadores NaP-IIb e PiT-1 no intestino delgado que não seguem um padrão uniforme. A sobrecarga de fósforo aumenta a porcentagem de enterócitos apoptóticos nos animais urêmicos / Phosphorus is one of the most abundant minerals in the body besides being essential for many biological processes. Phosphorus homeostasis depends on absorption in the small intestine, renal excretion, bone remodeling and hormones such as parathyroid hormone, calcitriol and FGF-23. In patients with chronic kidney disease phosphorus urinary excretion is compromised leading to hyperphosphatemia, which contributes to increased morbidity and mortality of these patients. Intestinal absorption of phosphorus in the small intestine, particularly of NaP-IIb and PiT-1 cotransporters is poorly studied. The aim of this study was to evaluate the effects of diets with different concentrations of phosphorus in protein expression and gene of NaP-IIb and PiT-1 cotransporters as well as in apoptosis of enterocytes of different segments of intestine in control and uremic animals. We studied seventy-six male Wistar rats initially divided into two groups: controls (C) and uremic (Nx). Each group was subdivided into three others, according to the phosphorus concentration in the diet: Low diet (0.2% P), Standard diet (0.54% P) and High diet (0.9% P). We analyzed biochemical parameters (creatinine, P, iCa, PTH and FGF-23), protein expression of cotransporters, using Western Blot, ELISA, immunofluorescence, real-time PCR and apoptosis of enterocytes using the TUNEL technique. Results showed that serum creatinine, P, PTH and FGF-23 were significantly higher in Nx animals. In C animals with a diet low in P we observed increase in protein expression of NaP-IIb cotransporter in all segments of the intestine while in low Nx expression of this cotransporter was lower only in jejunum. As for PiT-1 expression was lower in the ileum of the high Nx group compared to their respective control. Gene expression of NaP-IIb cotransporter was lower in the jejunum of high Nx and higher in the ileum of the same group as compared to their respective controls. PiT-1 gene expression was higher in all segments of the low Nx group compared to their controls. We detected a direct correlation between the gene expression of NaP-IIb in jejunum and serum phosphorus. Gene expression of PiT-1 correlated with serum phosphorus in the jejunum, and correlated with the serum levels of FGF-23 in the jejunum and duodenum. In the duodenum and jejunum the percentage of apoptotic enterocytes was higher in high Nx animals compared to controls; particularly in the duodenum the percentage of these cells was also higher in low Nx group and standard control. In the jejunum in both low Nx group and standard Nx we observed fewer apoptotic cells than in their respective controls. When we analyze all intestinal segments together the high Nx group had more apoptotic cells than the control, and the opposite was observed in the low Nx group and standard Nx group. In conclusion, diets with different phosphorus concentrations promote changes in protein expression and gene of NaP-IIb and PiT-1 cotransporters in the small intestine that do not follow a uniform pattern. Phosphorus overhead increases the percentage of apoptotic enterocytes in uremic animals

Le langage de Salvatore Sciarrino et celui de Brian Ferneyhough sembleraient aux antipodes : l’un doté d’une ligne épurée de tout excès, l’autre avec une notation surchargée de détails. La structure temporelle de leurs langages pourraient toutefois trouver un point de contact dans deux pièces pour flûte seule : L’orologio di Bergson de Sciarrino et Carceri d’Invenzione IIb de Ferneyhough. La pièce de Sciarrino est structurée sur la périodicité de certains éléments qui, par leur récurrence, créent une sensation de temps circulaire. Celle de Ferneyhough, bien que plus complexe à la surface, emploie la même idée de récurrence du matériau. La simplicité des éléments sonores de Sciarrino laisse la place à des unités de matériau incandescentes. Cette thèse a comme but de montrer une certaine similarité quant à la gestion du temps, et quant à son déroulement. L’analyse de plusieurs interprétations montrera aussi comment les interprètes s’approprient cette conception temporelle. / At first impression, the language of Salvatore Sciarrino and that of Brian Ferneyhough seem to be antipodes, two extremes exactly opposite to each other: one simple, pure, deprived of any unnecessary excess, while the other rich, complex, decorated with all the possible details. However, in these two pieces for flute solo, there is a common ground that can be found: L’orologio di Bergson of Salvatore Sciarrino and Carceri d’Invenzione IIb of Brian Ferneyhough. The piece of Sciarrino is structured on the periodicity of certain elements, by their recurrence, which create a sensation of circular time. While the piece of Ferneyhough, although, seemingly much more complex, employs the same idea of recurrence of the material. The simplicity of the sonic elements of Sciarrino gives the space to the unity of the incandescent materials. The objective of this thesis is to demonstrate some certain similarity, concerning the time management and its development. The analysis of several interpretation also shows how the interpreters adapt themselves to this time conception.

In the present project we study compactifications of type IIA/IIB string theories on toroidal orbifolds. We present the moduli space for N=1 four-dimensional reductions and its topological properties. To fix the value of all moduli, we will construct the most general holomorphic superpotential W using a set of T-dual iterations for the fluxes. Using a 3-torus toy-model, we will give an introductory description to the background of these generalised fluxes.

The long-term genetic consequences of supportive breeding programs are not well understood. Nevertheless, stocking populations with hatchery-produced fish to compensate for losses of natural production are common practice, for example after constructions of hydroelectric power dams. Hatcheries typically fertilize eggs using ‘mixed-milt fertilizations’, without consideration to natural reproductive behaviours, and hence, natural selective regimes would be altered. Here, a series of experiments with focus on Mhc and mate choice in a population of brown trout (Salmo trutta L.) with a history of long-term stocking are presented. The major histocompatibility complex (Mhc) constitutes of genes coding for antigen presentation in the vertebrate immune system. In addition to the immunological function, Mhc genes might also influence reproductive behaviours such as mate choice. For example, in some species individuals are able to recognize Mhc genotypes of potential mates and to some extent base their mate choice on this information. Here, I address these questions on brown trout. Can the phenomena be observed in brown trout? Could such mechanisms help individuals to avoid inbreeding, or are other mechanisms important? How does the artificial rearing of fish for enhancement of natural populations relate to these issues? The results presented here, in combination with previous work, shows that several factors are important in the process of pair formation in salmonid species. For example, females of the studied population used more than a single criterion when choosing among the available mates Mhc genes and males with certain Mhc genotypes achieved more matings, possibly an effect from increased fighting ability. Further, the population appears to contain an unnatural high level of Mhc variation, and some results indicate that the population might suffer from outbreeding depression at the Mhc. These negative effects are most likely derived from compression of sub-populations after dam-construction, in combination with supportive breeding with no consideration to natural spawning behaviour.

Thèse d'exercice : Médecine. Médecine générale : Paris 12 : 2005. / Titre provenant de l'écran-titre. Bibliogr. f. 81-93.

B lymphocytes play a significant role in autoimmune arthritis, with their function stretching beyond autoantibody production to cytokine secretion and presentation of autoantigen. However, the involvement and activation of different B-cell subset in the autoimmune response is not fully clear. The main focus of this thesis has been to understand the contribution of marginal zone (MZ) B cells in the induction of collagen-induced arthritis (CIA), a mouse model for rheumatoid arthritis (RA). We show that MZ B cells in the spleen of naïve mice display a natural self-reactivity to collagen type II (CII), the autoantigen used for immunization of CIA. The CII-reactive MZ B cells expand rapidly following immunization with CII, and produce IgM and IgG antibodies to CII. They also very efficiently present CII to cognate T cells in vitro and in vivo. Moreover, absence of regulatory receptors such as CR1/2 or FcγRIIb on the MZ B cells increases their proliferation and cytokine production in response to toll-like receptor, but not B-cell receptor, activation. Further, FcγRIIb-deficient MZ B cells present CII to T cells more efficiently than wild-type MZ B cells. We additionally demonstrate for the first time the existence of a small population of nodal MZ B cells in mouse lymph nodes. Similar to splenic MZ B cells, the nodal MZ B cells expand after CIA induction, secrete IgM anti-CII antibodies and can present CII to cognate T cells. Finally, we show that mast cells, associated with ectopic B cell follicles in inflamed RA joints, in coculture with B cells promote their expansion, production of IgM and IgG antibodies as well as upregulation of CD19 and L-selectin. Coculture with mast cells further causes the B cells to upregulate costimulators and class II MHC, important molecules for antigen-presenting function. In summary, my findings suggest that splenic and nodal self-reactive MZ B cells participate in breaking T-cell tolerance to CII in CIA. B-cell intrinsic regulation is needed to keep such autoreactive B cells quiescent. Mast cells can potentiate B-cell responses locally in the arthritic joint, thus feeding the autoimmune reaction.