Lessons from cardiac transplantation in infancy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73539/1/j.1399-3046.2009.01143.x.pd

Sand-spits systems from Benguela region (SW Angola). An analysis of sediment sources and dispersal from textural and compositional data

Sand spits are important coastline features in western Angola, but only limited knowledge on their recent evolution and sediment sources were obtained so far. The present study is focused on the Baía Farta and Lobito sand spits of coastal Benguela that develop to the north (i.e. downdrift) of the Coporolo and Catumbela river outlets. We used grain-size distributions, heavy-mineral suites and clay-mineral assemblages of sediments in the Coporolo-Baía Farta and Catumbela-Lobito coastal stretches to characterize the main depositional units and investigate sediment provenance. From the combined grain-size and mineralogical variability in mud and sand samples it is possible to infer sediment sources and dispersal in the two coastal stretches. Kaolinite is mainly derived from the Angola hinterland, and is particularly common in finer grained floodplain sediments from the Catumbela River. Expansive clays (smectite and illite-smectite mixed layers) are inferred to be mainly sourced by Meso-Cenozoic units of the Benguela Basin, being abundant in coarser grained fluvial deposits and in lagoonal deposits near Baía Farta. Sand supplied by the sedimentary units from Benguela Basin and their basement rocks tends to be enriched in epidote associated with blue-green hornblende. The Coporolo River sand is progressively diluted during the longshore northward transport by sand supplied by coastal units. Conversely, beach deposits in the Catumbela-Lobito coastal stretch are mainly sourced by the Catumbela River. A divergent longshore transport from Catumbela river-mouth occurs at Catumbela delta. Sand spit morphology and evolution reflect the patterns of dispersal of bedload and suspended load in settings of contrasting orography and human influence

Toward a solution for cardiac failure in the newborn

The newborn infant with severe cardiac failure owed to congenital structural heart disease or cardiomyopathy poses a daunting therapeutic challenge. The ideal solution for both might be cardiac transplantation if availability of hearts was not limiting and if tolerance could be induced, obviating toxicity of immunosuppressive therapy. If one could safely and effectively exploit neonatal tolerance for successful xenotransplantation of the heart, the challenge of severe cardiac failure in the newborn infant might be met. We discuss the need, the potential for applying neonatal tolerance in the setting of xenotransplantation and the possibility that other approaches to this problem might emerge.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146972/1/xen12479.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146972/2/xen12479_am.pd

Short-lived and Long-lived Bone Marrow Plasma Cells Are Derived from a Novel Precursor Population

The contribution that long-lived bone marrow (BM) plasma cells (PCs) provide to enduring humoral immunity has been underscored by a number of recent studies. However, little is known about the immediate precursors that give rise to long-lived PCs in the BM of immune individuals. We have identified subsets of antigen-experienced B cells within the immune BM that are precursors to PCs. These PC precursors arise in the BM 14 days after immunization and persist for greater than 9 months. Phenotypically distinct subsets of PC precursors give rise to short-lived or long-lived PCs. The differentiation of PC precursors to PCs occurs in the absence of antigen and requires cell division. The functional significance of these newly identified PC precursors in the persistence and quality of the humoral immune response is discussed

Histone H2A and H2B Are Monoubiquitinated at AID-Targeted Loci

Background: Somatic hypermutation introduces base substitutions into the rearranged and expressed immunoglobulin (Ig) variable regions to promote immunity. This pathway requires and is initiated by the Activation Induced Deaminase (AID) protein, which deaminates cytidine to produce uracils and UG mismatches at the Ig genes. Subsequent processing of uracil by mismatch repair and base excision repair factors contributes to mutagenesis. While selective for certain genomic targets, the chromatin modifications which distinguish hypermutating from non-hypermutating loci are not defined. Methodology/Principal Findings: Here, we show that AID-targeted loci in mammalian B cells contain ubiquitinated chromatin. Chromatin immunoprecipitation (ChIP) analysis of a constitutively hypermutating Burkitt\u27s B cell line, Ramos, revealed the presence of monoubiquitinated forms of both histone H2A and H2B at two AID-associated loci, but not at control loci which are expressed but not hypermutated. Similar analysis using LPS activated primary murine splenocytes showed enrichment of the expressed V(H) and S gamma 3 switch regions upon ChIP with antibody specific to AID and to monoubiquitinated H2A and H2B. In the mechanism of mammalian hypermutation, AID may interact with ubiquitinated chromatin because confocal immunofluorescence microscopy visualized AID colocalized with monoubiquitinated H2B within discrete nuclear foci. Conclusions/Significance: Our results indicate that monoubiquitinated histones accompany active somatic hypermutation, revealing part of the histone code marking AID-targeted loci. This expands the current view of the chromatin state during hypermutation by identifying a specific nucleosome architecture associated with somatic hypermutation

Inflammation-induced formation of fat-associated lymphoid clusters

Fat-associated lymphoid clusters (FALCs) are a type of lymphoid tissue associated with visceral fat. Here we found that the distribution of FALCs was heterogeneous, with the pericardium containing large numbers of these clusters. FALCs contributed to the retention of B-1 cells in the peritoneal cavity through high expression of the chemokine CXCL13, and they supported B cell proliferation and germinal center differentiation during peritoneal immunological challenges. FALC formation was induced by inflammation, which triggered the recruitment of myeloid cells that expressed tumor-necrosis factor (TNF) necessary for signaling via the TNF receptors in stromal cells. Natural killer T cells (NKT cells) restricted by the antigen-presenting molecule CD1d were likewise required for the inducible formation of FALCs. Thus, FALCs supported and coordinated the activation of innate B cells and T cells during serosal immune responses

Cryptic B Cell Response to Renal Transplantation

Transplantation reliably evokes allo‐specific B cell and T cell responses in mice. Yet, human recipients of kidney transplants with normal function usually exhibit little or no antibody specific for the transplant donor during the early weeks and months after transplantation. Indeed, the absence of antidonor antibodies is taken to reflect effective immunosuppressive therapy and to predict a favorable outcome. Whether the absence of donor‐specific antibodies reflects absence of a B cell response to the donor, tolerance to the donor or immunity masked by binding of donor‐specific antibodies to the graft is not known. To distinguish between these possibilities, we devised a novel ELISPOT, using cultured donor, recipient and third‐party fibroblasts as targets. We enumerated donor‐specific antibody‐secreting cells in the blood of nine renal allograft recipients with normal kidney function before and after transplantation. Although none of the nine subjects had detectable donor‐specific antibodies before or after transplantation, all exhibited increases in the frequency of donor‐specific antibody‐secreting cells eight weeks after transplantation. The responses were directed against the donor HLA‐class I antigens. The increase in frequency of donor‐specific antibody‐secreting cells after renal transplantation indicates that B cells respond specifically to the transplant donor more often than previously thought. The authors report that clinical transplantation evokes an appreciable B cell response in most, if not all, transplant recipients, raising the prospect that accommodation might be a more common outcome than previously thought. See editorial by Clatworthy on page 1629.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98816/1/ajt12308.pd