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Medieval Ceramics: Journal of the Medieval Ceramics Research Group, 14, 57-57

Medieval Ceramics: Journal of the Medieval Ceramics Research Group, 15, 29-36, This paper examines the evidence for the use and probable re-introduction of pottery in the southern Welsh borderland following the Norman conquest, based on discoveries in Monnow Street, Monmouth and material from previous excavations in the area. Burgages in Monnow Street contain a remarkably well-preserved series of medieval house floors dating from shortly after the Conquest, which have provided a 'key' to the pottery sequences in the town, especially for the period c.AD 1100 to 1400. A summary of regional assemblages containing D2 Cotswold ware is also presented.

Medieval Ceramics: Journal of the Medieval Ceramics Research Group, 16, 72-76

Infection with Staphylococcus aureus does not induce long-lived protective immunity for reasons that are not completely understood. Human and murine vaccine studies support a role for antibodies in protecting against recurring infections, but S. aureus modulates the B cell response through expression of Staphylococcal Protein A (SpA), a surface protein that drives polyclonal B cell expansion and induces cell death in the absence of co-stimulation. In this murine study, we show that SpA altered the fate of plasmablasts and plasma cells (PCs) by enhancing the short-lived extrafollicular response and reducing the pool of bone marrow (BM)-resident long-lived PCs (LLPCs). The absence of LLPCs was associated with a rapid decline in antigen-specific, class-switched antibody. In contrast, when previously inoculated mice were challenged with isogenic Δspa S. aureus, cells proliferated in the BM survival niches and sustained long-term antibody titers. The effects of SpA on PC fate were limited to the secondary response, as antibody levels and the formation of B cell memory occurred normally during the primary response in mice inoculated with either WT or Δspa S. aureus. Thus, failure to establish long-term protective antibody titers against S. aureus was not a consequence of diminished formation of B cell memory; instead, SpA reduced the proliferative capacity of PCs that entered the BM, diminishing the number of cells in the long-lived pool.

Ab-secreting plasma cells (PCs) are the effectors of humoral immunity. In this study, we describe regulation of autoreactive B cells specific for the ribonucleoprotein Smith (Sm) at an early pre-PC stage. These cells are defined by the expression of the PC marker CD138 and normal levels of CD19 and B220. They are present at a high frequency in normal mouse spleen and bone marrow, are Ag dependent, and are located predominantly along the T cell-B cell border and near bridging channels. Anti-Sm pre-PCs also occur at a high frequency in nonautoimmune mice and show additional phenotypic characteristics of PC differentiation. However, while some of these pre-PCs are Ab-secreting cells, those specific for Sm are not, indicating regulation. Consistent with this, anti-Sm pre-PCs have a higher turnover rate and higher frequency of cell death than those that do not bind Sm. Regulation of anti-Sm pre-PCs occurs upstream of the transcriptional repressor, B lymphocyte-induced maturation protein-1, expression. Regulation at this stage is overcome in autoimmune MRL/lpr mice and is accompanied by an altered B lymphocyte stimulator receptor profile. These data reveal a new B cell tolerance checkpoint that is overcome in autoimmunity.

Polyclonal B cell activation promotes immunity without the loss of tolerance. Our data show that during activation of the innate immune system, B cell tolerance to Smith Ag Sm is maintained by dendritic cells (DCs) and macrophages (MPhi). TLR4-activated myeloid DCs and MPhi, but not plasmacytoid or lymphoid DCs, repressed autoreactive B cells through the secretion of soluble mediators, including IL-6. Although IL-6 promotes plasma cell differentiation of B cells acutely stimulated by Ag, we show that it repressed cells that were chronically exposed to self-Ag. This mechanism of tolerance was not limited to Smith Ag-specific B cells as hen egg lysozyme- and p-azophenylarsonate-specific B cells were similarly affected. Our data define a tolerogenic role for MPhi and DCs in regulating autoreactive B cells during activation of the innate immune system.

Medieval Archaeology, 47, 186-189, Short report of a watching brief on groundworks on the hillside below the Norman castle during 2001. A large V-shaped ditch was uncovered, running roughly in line with the ridge and producing a small assemblage of medieval cooking pottery dating from the twelfth century. This and evidence from other sites indicate that Abergavenny was an early Norman defended settlement.

Phosphatidyl choline (PtC)-specific B cells segregate to the B-1 subset, where they comprise up to 10% of the B-1 repertoire. About half express VH12 and Vκ4/5H and are restricted in VHCDR3. We have previously reported that anti-PtC VHCDR3 is enriched among VH12-expressing cells by selective elimination of pre-B cells. We report here a bias for Vκ4/5H expression among VH12-expressing B cells, even among those that do not bind PtC and are not B-1. This is due in part to an inability of VH12 to associate with many light (L) chains but must also be due to a selective advantage in survival or clonal expansion in the periphery for Vκ4/5H-expressing cells. Thus, the bias for Vκ4/5H expression is independent of PtC binding, and, as segregation to B-1 occurs after Ig gene expression, it precedes segregation to the B-1 subset. In 6-1 mice, splenic B-1 cells reside in follicles but segregate to follicles distinct from those that contain B-2 cells. These data indicate that selection at multiple developmental checkpoints ensures the co-expression of an anti-PtC VHCDR3 and L chain in a high frequency of VH12 B cells. This focus toward specificity for PtC facilitates the development of a large anti-PtC B-1 repertoire.