Temporary labor migration and domestic economy in social reproduction strategies: the case of forest workers Bernardo de Irigoyen (Misiones, Argentina)

El objetivo de este artículo es analizar cómo las unidades domésticas participes de la migración laboral temporaria articulan distintos mecanismos de reproducción social, haciendo énfasis en el lugar que ocupan las prácticas agropecuarias a pequeña escala. Nuestro referente empírico es un conjunto de unidades domésticas ubicadas en la zona rural del municipio de Bernardo de Irigoyen (Misiones, Argentina) que cuentan con algún/os miembros que migran o han migrado hacía otras provincias para emplearse en el sector forestal. La metodología empleada es de tipo cualitativa mediante la utilización de entrevistas a miembros migrantes y no migrantes de las unidades domésticas analizadas, complementadas con observaciones. Este artículo concluye que en aquellos grupos domésticos con mayores dificultades de inserción al mercado laboral, las prácticas agropecuarias, junto con las transferencias monetarias estatales, son centrales en la reproducción social. Por el contrario, en aquellos casos en que algún miembro de la unidad doméstica sostiene una inserción al mercado laboral relativamente estable, las prácticas prediales tienen una importancia secundaria o nula para la subsistencia del grupo. Asimismo, las distintas formas de configuración de estrategias de reproducción varían según las características de la unidad doméstica y se vinculan con distintas formas de división familiar del trabajo, prácticas de consumo y estrategias de escolarización.The objective of this article is to analyze how domestic units participating in temporary labor migration articulate different mechanisms of social reproduction, emphasizing the place of small-scale farming practices. Our empirical reference is a set of domestic units located in the rural area of the municipality of Bernardo de Irigoyen (Misiones, Argentina) that have some members who migrate or have migrated to other provinces to be employed in the forestry sector. The methodology used is qualitative by using interviewees to migrant and non-migrant members of the domestic units analyzed, complemented by observations. This article concludes that in those groups with greater diffi culties of insertion in the labor market, the agricultural practices, together with the state monetary transfers, the threads in the social reproduction. On the contrary, in cases where a member of the household maintains an insertion in the stable labor market, property practices are of secondary importance to the subsistence of the group. Also, the diverse forms of confi guration of reproduction strategies vary according to the characteristics of the household and relate to different forms of family division of labor, consumption practices and schooling strategies.Fil: Albertí, Alfonsina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro de Estudios e Investigaciones Laborales; Argentin

Bruton's Tyrosine Kinase Cooperates with the B Cell Linker Protein SLP-65 as a Tumor Suppressor in Pre-B Cells

Expression of the pre-B cell receptor (pre-BCR) leads to activation of the adaptor molecule SLP-65 and the cytoplasmic kinase Btk. Mice deficient for one of these signaling proteins have an incomplete block in B cell development at the stage of large cycling pre-BCR+CD43+ pre-B cells. Our recent findings of defective SLP-65 expression in ∼50% of childhood pre-B acute lymphoblastic leukemias and spontaneous pre-B cell lymphoma development in SLP-65−/− mice demonstrate that SLP-65 acts as a tumor suppressor. To investigate cooperation between Btk and SLP-65, we characterized the pre-B cell compartment in single and double mutant mice, and found that the two proteins have a synergistic role in the developmental progression of large cycling into small resting pre-B cells. We show that Btk/SLP-65 double mutant mice have a dramatically increased pre-B cell tumor incidence (∼75% at 16 wk of age), as compared with SLP-65 single deficient mice (<10%). These findings demonstrate that Btk cooperates with SLP-65 as a tumor suppressor in pre-B cells. Furthermore, transgenic low-level expression of a constitutive active form of Btk, the E41K-Y223F mutant, prevented tumor formation in Btk/SLP-65 double mutant mice, indicating that constitutive active Btk can substitute for SLP-65 as a tumor suppressor

Rearrangement and Expression of Immunoglobulin Light Chain Genes Can Precede Heavy Chain Expression during Normal B Cell Development in Mice

In mouse mutants incapable of expressing μ chains, VκJκ joints are detected in the CD43+ B cell progenitors. In agreement with these earlier results, we show by a molecular single cell analysis that 4–7% of CD43+ B cell progenitors in wild-type mice rearrange immunoglobulin (Ig)κ genes before the assembly of a productive VHDHJH joint. Thus, μ chain expression is not a prerequisite to Igκ light chain gene rearrangements in normal development. Overall, ∼15% of the total CD43+ B cell progenitor population carry Igκ gene rearrangements in wild-type mice. Together with the results obtained in the mouse mutants, these data fit a model in which CD43+ progenitors rearrange IgH and Igκ loci independently, with a seven times higher frequency in the former. In addition, we show that in B cell progenitors VκJκ joining rapidly initiates κ chain expression, irrespective of the presence of a μ chain

Immunoglobulin expression in the endoplasmic reticulum shapes the metabolic fitness of B lymphocytes

The major function of B lymphocytes is to sense antigens and to produce protective antibodies after activation. This function requires the expression of a B-cell antigen receptor (BCR), and evolutionary conserved mechanisms seem to exist that ensure that B cells without a BCR do not develop nor survive in the periphery. Here, we show that the loss of BCR expression on Burkitt lymphoma cells leads to decreased mitochondrial function and impaired metabolic flexibility. Strikingly, this phenotype does not result from the absence of a classical Syk-dependent BCR signal but rather from compromised ER expansion. We show that the reexpression of immunoglobulins (Ig) in the absence of the BCR signaling subunits Igα and Igβ rescues the observed metabolic defects. We demonstrate that immunoglobulin expression is needed to maintain ER homeostasis not only in lymphoma cells but also in resting B cells. Our study provides evidence that the expression of BCR components, which is sensed in the ER and shapes mitochondrial function, represents a novel mechanism of metabolic control in B cells

Kidins220/ARMS binds to the B cell antigen receptor and regulates B cell development and activation

B cell antigen receptor (BCR) signaling is critical for B cell development and activation. Using mass spectrometry, we identified a protein kinase D\u2013interacting substrate of 220 kD (Kidins220)/ankyrin repeat\u2013rich membrane-spanning protein (ARMS) as a novel interaction partner of resting and stimulated BCR. Upon BCR stimulation, the interaction increases in a Src kinase\u2013independent manner. By knocking down Kidins220 in a B cell line and generating a conditional B cell\u2013specific Kidins220 knockout (B-KO) mouse strain, we show that Kidins220 couples the BCR to PLC\u3b32, Ca2+, and extracellular signal-regulated kinase (Erk) signaling. Consequently, BCR-mediated B cell activation was reduced in vitro and in vivo upon Kidins220 deletion. Furthermore, B cell development was impaired at stages where pre-BCR or BCR signaling is required. Most strikingly, \u3bb light chain\u2013positive B cells were reduced sixfold in the B-KO mice, genetically placing Kidins220 in the PLC\u3b32 pathway. Thus, our data indicate that Kidins220 positively regulates pre-BCR and BCR functionin

Gene conversion in human rearranged immunoglobulin genes

Over the past 20 years, many DNA sequences have been published suggesting that all or part of the V&lt;sub&gt;H&lt;/sub&gt; segment of a rearranged immunoglobulin gene may be replaced in vivo. Two different mechanisms appear to be operating. One of these is very similar to primary V(D)J recombination, involving the RAG proteins acting upon recombination signal sequences, and this has recently been proven to occur. Other sequences, many of which show partial V&lt;sub&gt;H&lt;/sub&gt; replacements with no addition of untemplated nucleotides at the V&lt;sub&gt;H&lt;/sub&gt;–V&lt;sub&gt;H&lt;/sub&gt; joint, have been proposed to occur by an unusual RAG-mediated recombination with the formation of hybrid (coding-to-signal) joints. These appear to occur in cells already undergoing somatic hypermutation in which, some authors are convinced, RAG genes are silenced. We recently proposed that the latter type of V&lt;sub&gt;H&lt;/sub&gt; replacement might occur by homologous recombination initiated by the activity of AID (activation-induced cytidine deaminase), which is essential for somatic hypermutation and gene conversion. The latter has been observed in other species, but not in human Ig genes, so far. In this paper, we present a new analysis of sequences published as examples of the second type of rearrangement. This not only shows that AID recognition motifs occur in recombination regions but also that some sequences show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species. These observations support the proposal that this type of rearrangement is likely to be AID-mediated rather than RAG-mediated and is consistent with gene conversion

A barcoded flow cytometric assay to explore the antibody responses against SARS-CoV-2 spike and its variants

The SARS-CoV-2 pandemic has spread to all parts of the world and can cause life-threatening pneumonia and other severe disease manifestations known as COVID-19. This health crisis has resulted in a significant effort to stop the spread of this new coronavirus. However, while propagating itself in the human population, the virus accumulates mutations and generates new variants with increased fitness and the ability to escape the human immune response. Here we describe a color-based barcoded spike flow cytometric assay (BSFA) that is particularly useful to evaluate and directly compare the humoral immune response directed against either wild type (WT) or mutant spike (S) proteins or the receptor-binding domains (RBD) of SARS-CoV-2. This assay employs the human B lymphoma cell line Ramos, transfected for stable expression of WT or mutant S proteins or a chimeric RBD-CD8 fusion protein. We find that the alpha and beta mutants are more stably expressed than the WT S protein on the Ramos B cell surface and/or bind with higher affinity to the viral entry receptor ACE2. However, we find a reduce expression of the chimeric RBD-CD8 carrying the point mutation N501Y and E484K characteristic for the alpha and beta variant, respectively. The comparison of the humoral immune response of 12 vaccinated probands with 12 COVID-19 patients shows that after the boost, the S-specific IgG class immune response in the vaccinated group is similar to that of the patient group. However, in comparison to WT the specific IgG serum antibodies bind less well to the alpha variant and only poorly to the beta variant S protein. This is in line with the notion that the beta variant is an immune escape variant of SARS-CoV-2. The IgA class immune response was more variable than the IgG response and higher in the COVID-19 patients than in the vaccinated group. In summary, we think that our BSFA represents a useful tool to evaluate the humoral immunity against emerging variants of SARS-CoV-2 and to analyze new vaccination protocols against these variants

Expression of excess receptors and negative feedback control of signal pathways are required for rapid activation and prompt cessation of signal transduction

Cellular signal transduction is initiated by the binding of extracellular ligands to membrane receptors. Receptors are often expressed in excess, and cells are activated when a small number of receptors bind ligands. Intracellular signal proteins are act