Bestelako eskola eredu bat posible da: bizilore, eskola komunitate berri baten lehen urratsak

Hoy en día, y aunque el proceso sea lento, emergen, cada vez con más fuerza, voces y experiencias a favor de un modelo de escuela en el que, entre otras cuestiones, el alumnado no aprende solo lo que el profesorado le enseña, ni todos los participantes tienen por qué conseguir los mismos objetivos. Este artículo nos lleva a reflexionar en torno a este otro modelo de escuela, a través de la investigación etnográfica de la experiencia que están viviendo en la escuela Bizilore de Azkoitia. La investigación se desarrolla a partir de la observación participante de la vida cotidiana, de las conversaciones con el profesorado, de madres y padres, y de la revisión de la documentación. Todo ello se pone en discusión con las aportaciones de diferentes autores de referencia y con otras experiencias. Entre las conclusiones, se identifican las bases pedagógicas de una escuela activa centrada en el bienestar de la niña y el niño y se identifican las posibilidades de su puesta en práctica.; Gaur egunean, gero eta gehiago, bestelako eskola eredu baten aldeko aldarriak eta esperientziak loratzen ari dira batean eta bestean. Besteak beste, eta mantso bada ere, ikasleak ez du irakasleak erakusten diona bakarrik ikasten; edota ikasle talde bateko partaideek mugarri berbera lortu beharra ere, indarra galtzen ari da. Gradu Amaierako Lan honek, Azkoitiko Bizilore eskola aktiboan bizi duten esperientziaren ikerketa kualitatiboaren bitartez, bestelako eskola eredu baten inguruan hausnarketa egitera eramaten gaitu. Ikerketa, eskolako eguneroko bizitzaren behaketa parte-hartzailean, irakasle eta gurasoen elkarrizketetan eta dokumentazioan oinarritzen da. Hori guztia, gaiaren inguruan erreferentziazko autore desberdinek eta esperientziek egiten dituzten ekarpenekin eztabaidan jarri da. Ondorioen artean, haurraren ongizatean oinarritutako eskola aktibo baten oinarri pedagogikoak identifikatu eta praktikara eramateko aukerak aztertu dira.; We are witnessing in the present a progressive emergence of new and stronger voices and experiences supporting a new model of school where the students won’t just learn what they are taught by their teacher, or where everyone won’t be oriented to the achievement of some established goals. The present research analyzes the case study of "Bizilore eskola" in Azkoitia (Gipuzkoa), focusing on the relevance this new model of school we mentioned before entails.The research has been carried out considering and analyzing the data obtained from a participative fieldwork where several issues and situations with parents, teachers and paperwork have been tackled. The compiled data has been later contextualized considering the contribution of some relevant authors and theories. Among the conclusions, we can identify some pedagogical basis of active schools oriented to the welfare of the kids. We also consider the possibility of putting into practice the aforementioned basis

Dissecting Integrin Expression and Function on Memory B Cells in Mice and Humans in Autoimmunity

Immunological memory ensures life-long protection against previously encountered pathogens, and in mice and humans the spleen is an important reservoir for long-lived memory B cells (MBCs). It is well-established that integrins play several crucial roles in lymphocyte survival and trafficking, but their involvement in the retention of MBCs in secondary lymphoid organs, and differences between B cell subsets in their adhesion capacity to ICAM-1 and/or VCAM-1 have not yet been confirmed. Here, we use an autoimmune mouse model, where MBCs are abundant, to show that the highest levels of LFA-1 and VLA-4 amongst B cells are found on MBCs. In vivo blockade of VLA-4 alone or in combination with LFA-1, but not LFA-1 alone, causes a release of MBCs from the spleen into the blood stream. In humans, we find that in peripheral blood, spleens, and tonsils from healthy donors the highest expression levels of the integrins LFA-1 and VLA-4 are also found on MBCs. Consistent with this, we found MBCs to have a higher capacity to adhere to ICAM-1 and VCAM-1 than naïve B cells. In patients with the autoimmune disease rheumatoid arthritis, it is the MBCs that have the highest levels of LFA-1 and VLA-4; moreover, compared with healthy donors, naïve B and MBCs of patients receiving anti-TNF medication have enhanced levels of the active form of LFA-1. Commensurate levels of the active αL subunit can be induced on B cells from healthy donors by exposure to the integrin ligands. Thus, our findings establish the selective use of the integrins LFA-1 and VLA-4 in the localization and adhesion of MBCs in both mice and humans

The Interplay between CD27dull and CD27bright B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory

Summary: Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27dull and CD27bright MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property changes, reflecting consecutive selection of highly antigen-specific, low cross-reactive antibody variants, all demonstrate that CD27dull and CD27bright MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27dull into the CD27bright MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27dull MBCs transit to the more differentiated CD27bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27dull clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27dull MBCs that expand and differentiate in response to change. : Grimsholm et al. show that CD27dull and CD27bright represent sequential MBC developmental stages. T cell- and germinal center (GC)-independent CD27dull MBCs are the plastic source of strongly selected and GC-dependent CD27bright MBCs. CD27dull MBCs, able to expand and differentiate in response to change, ensure stability and flexibility of human B cell memory. Keywords: memory B cells, pregnancy, immunological memory, CD27, VH repertoire, immunodeficiency, aging, spleen, vaccine, germinal cente

Studies of penta-decameric binding proteins: AP-4 and CBF-A

Each immunoglobulin (Ig) V gene segment contains an upstream promoter region. The octamer element and the TATA box are the only elements that are conserved in all Ig promoters. The presence of the octamer element is necessary, but not sufficient to support high levels of transcription. Therefore, the activity of other co-stimulatory elements is required. This investigation has focused on the study of one such regulatory region: the penta-decameric (pd) element. The pd element is an integral part of the SP6 V-kappa promoter and shows functional synergism with the octamer element at the late stages in B cell differentiation. The pd element is comprised of an E2A type of E-box (5’-CAGCTG-3-) and an AT-rich region. Previous work had identified CArG box-binding factor-A (CBF-A) as the protein interacting with the AT-rich moiety. However, the ligand for the E-box was an unknown. Our work has now identified the bHLH-Zip protein AP-4 as the E-box binding factor. In addition, AP-4 has been found to bind to the second E-box (5’-CAGCTG-3’) found 3’ from the octamer site. E-boxes are conserved within human V-kappa promoter subgroups I, III, IV, V and VII, and related families, hence reinforcing the idea that the natural ligand for Ig-kappa promoter E-boxes is AP-4. Lastly, we pursued the study of CBF-A by searching for interacting partners by using a yeast Two-Hybrid screen. We have now characterised two important proteins interacting with CBF-A, the nucleolar phosphoprotein nucleophosmin(NPM/B23) and hnRNP H. Furthermore, CBF-A shows selectivity in its interactions, since CBF-A/NPM complexes are detected in the nucleus only, as opposed to the cytoplasmic only CBF-A/hnRNP H heterotypic complexes. Interestingly, we have shown that CBF-A undergoes self-oligomerisation in both the nuclear and cytoplasmic compartments. In addition, we have evidence to suggest that CBF-A might be shuttling between the nucleus and the cytoplasm. Specifically, we show that mitogenic stimulation of resting B cells promotes CBF-A accumulation in the nucleus. We have mapped the region responsible for the import/export activity of CBF-A to the most carboxyl-terminal 13 amino acid residues

TLR Ligation Triggers Somatic Hypermutation in Transitional B Cells Inducing the Generation of IgM Memory B Cells

AbstractTLR9 activation by unmethylated CpG provides a homeostatic mechanism to maintain B cell memory in the absence of Ag. In this study, we demonstrate that CpG also triggers the generation of somatically mutated memory B cells from immature transitional B cells. In response to CpG, a fraction of transitional B cells proliferates and introduces somatic hypermutations in the H chain V regions. The nonproliferating pool of transitional B cells mostly maintains germline configurations. Mutations are VH specific: VH5 is the least mutated family, whereas VH1 and VH4/6 are the most mutated families. CpG stimulation also results in upregulation of VH5 transcripts in proliferating cells. Therefore, early recognition of bacterial DNA preferentially expands VH5-expressing B cells while inducing somatic hypermutations in other families. The mutation frequency, range, and type of substitutions observed in vitro are comparable to those found in memory B cells from the peripheral blood of Hyper IgM type 1 patients and the spleen of normal infants. The process triggered by TLRs may represent a first step leading to additional diversification of the germline repertoire and to the generation of memory B cells that will further refine their repertoire and specificity in the germinal centers

Human B-cell memory is shaped by age- and tissue-specific T-independent and GC-dependent events

Switched and IgM memory B cells execute different and noninterchangeable functions. We studied memory B cells in children of different ages, in peripheral blood and spleen and compared them with those of children born asplenic or unable to build germinal centers. We show that, whereas switched memory B cells are mostly generated in the germinal centers at all ages, IgM memory B cells can be distinct in three types with different developmental history. Innate IgM memory B cells, the largest pool in infants, are generated in the spleen by a germinal center-independent mechanism. With age, if the spleen is present and germinal centers are functional, innate IgM memory B cells are remodelled and accumulate somatic mutations. The third type of IgM memory B cell is a by-product of the germinal center reaction. Our data suggest that the B-cell memory developmental program is implemented during the first 5-6 years of life

Human CD38 regulates B cell antigen receptor dynamic organization in normal and malignant B cells

CD38 is a multifunctional protein expressed on the surface of B cells in healthy individuals but also in B cell malignancies. Previous studies have suggested a connection between CD38 and components of the IgM class B cell antigen receptor (IgM-BCR) and its coreceptor complex. Here, we provide evidence that CD38 is closely associated with CD19 in resting B cells and with the IgM-BCR upon engagement. We show that targeting CD38 with an antibody, or removing this molecule with CRISPR/Cas9, inhibits the association of CD19 with the IgM-BCR, impairing BCR signaling in normal and malignant B cells. Together, our data suggest that CD38 is a new member of the BCR coreceptor complex, where it exerts a modulatory effect on B cell activation upon antigen recognition by regulating CD19. Our study also reveals a new mechanism where α-CD38 antibodies could be a valuable option in therapeutic approaches to B cell malignancies driven by aberrant BCR signaling