Human Peripheral Blood Mononuclear Cells Exhibit Heterogeneous CD52 Expression Levels and Show Differential Sensitivity to Alemtuzumab Mediated Cytolysis

Alemtuzumab is a monoclonal antibody that targets cell surface CD52 and is effective in depleting lymphocytes by cytolytic effects in vivo. Although the cytolytic effects of alemtuzumab are dependent on the density of CD52 antigen on cells, there is scant information regarding the expression levels of CD52 on different cell types. In this study, CD52 expression was assessed on phenotypically distinct subsets of lymphoid and myeloid cells in peripheral blood mononuclear cells (PBMCs) from normal donors. Results demonstrate that subsets of PBMCs express differing levels of CD52. Quantitative analysis showed that memory B cells and myeloid dendritic cells (mDCs) display the highest number while natural killer (NK) cells, plasmacytoid dendritic cells (pDCs) and basophils have the lowest number of CD52 molecules per cell amongst lymphoid and myeloid cell populations respectively. Results of complement dependent cytolysis (CDC) studies indicated that alemtuzumab mediated profound cytolytic effects on B and T cells with minimal effect on NK cells, basophils and pDCs, correlating with the density of CD52 on these cells. Interestingly, despite high CD52 levels, mDCs and monocytes were less susceptible to alemtuzumab-mediated CDC indicating that antigen density alone does not define susceptibility. Additional studies indicated that higher expression levels of complement inhibitory proteins (CIPs) on these cells partially contributes to their resistance to alemtuzumab mediated CDC. These results indicate that alemtuzumab is most effective in depleting cells of the adaptive immune system while leaving innate immune cells relatively intact

Assemblage variability and bifacial points in the lowermost Sibudan layers at Sibudu, South Africa

Building on the important work of Lyn Wadley at Sibudu, archeologists from the University of Tübingen have excavated the upper stratigraphic units of the Middle Stone Age (MSA) sequence down to the Howiesons Poort (HP). Here, we present the main results from lithic analyses of the lowest part of the Sibudan sequence to assess its overall variability and taxonomic status. Based on the new findings, we also discuss the implications for archeological systematics and the cultural evolution of modern humans in MIS 3 from a more general perspective. The Sibudan deposits encompass over 20 archeological horizons that span a 1.2-m-thick, well-stratified sequence whose base and top have been dated to ∼58 ka (MIS 3). In contrast to the upper stratigraphic units, the lower Sibudan assemblages that we analyzed here show much higher use of local sandstone, quartz, and quartzite. These older units are characterized by frequent use of expedient core reduction methods, bipolar reduction of locally available quartz and quartzite, less retouch of blanks, and lower find densities. Tongati and Ndwedwe tools, which feature abundantly in the upper part of the Sibudan sequence, are entirely absent, as are unifacial points. Instead, notched and denticulated tools are common. Surprisingly, knappers manufactured small bifacial points, mainly made from quartz, by means of alternating shaping in the course of the oldest occupations. The results highlight the great diversity of human technological behavior over even short periods during the MSA, raising important questions about the mechanisms of behavioral change, cultural taxonomy, appropriate scales of lithic analyses, and the relationship between the HP and the Sibudan. Our findings further erode the old idea that bifacial technology in southern Africa is limited to the Still Bay. Research is increasingly showing that bifacial points come and go in different forms and contexts of African Late Pleistocene technology, impeding their use as chrono-cultural markers