Richard Hardy

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..The relationship of normal B-1 cells with B-cell lymphomas and leukemias continues to be a subject of interest and debate...

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..Together, these constrain VH11 generation to fetal development and may favor production of B cells with the prototype VH11Vkappa9 BCR...

..Increasingly powerful flow cytometry analysis of genetically altered animals (knockouts and transgenics) combined with sensitive functional assays may provide an answer, a "scorecard" for the cell stages...

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..The consequence is very distinct primary repertoires for development of fetal B1 cells and adult bone marrow B2 cells...

..Finally, we describe a new VH3609 antithymocyte Ig transgenic mouse model system that has provided the first definitive evidence for the role of self-antigen in development and maintenance of natural autoreactive B cells...

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..Furthermore, we suggest that such distinct programs of class II expression during fetal and adult lymphopoiesis could result in differences in susceptibility to tolerance...

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..Thus, B cells can be subject to positive selection, generated, and maintained on the basis of their autoreactivity...

..Thus, heterogeneity of Valpha14+ T cell reactivity is due to both beta-chain diversity and control mechanism(s) beyond primary TCR structure...

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..This is the first genetic defect of its kind to be described in the mouse and may prove highly informative in understanding the molecular pathways underlying lineage commitment...

..EBF function was enhanced by interaction with the transcription factor Runx1. These data suggest a molecular basis for the hierarchical dependence of Pax5 function on EBF and E2A in B lymphocyte development...

..g., size and internal granularity) and correlated expression of several surface molecules...

..These findings support a model whereby Ag-induced receptor editing is inhibited by BCR basal signaling on developing B cells; BCR down-regulation removes this basal signal, thereby initiating receptor editing...

..Here, we examine another possible bottleneck to the B1 cell repertoire: light chain pairing with V(H)11 heavy chain, finding very significant preferences...

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..Thus, Cbl proteins control B cell-intrinsic checkpoint of immune tolerance, possibly through coordinating multiple BCR-proximal signaling pathways during anergy induction...

..Our findings provide an animal model for CLL, the most common human leukemia, and demonstrate that deregulation of the Tcl1 pathway plays a crucial role in CLL pathogenesis...

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..These studies identify a previously unappreciated level of plasticity in the B cell developmental program, and have important implications for our understanding of central tolerance mechanisms...

..These results indicate that B-1 B cells are the first B cells to express fully mature levels of CXCR5, thereby promoting the development of FDC...

..These findings demonstrate that B-1 positive selection, resulting in the production of natural serum ATA, arises independently from the major pathway of BM B cell development and selection...

..A) stage, and B/T lymphoid plasticity persists until the CD19+ pro-B stage. Thus, MLP, CLP, and Fr. A represent progressively B lineage-specified stages in development, before the CD19+ B lineage-committed pro-B stage...

..These data indicate that positive selection can occur in developing B cells and that BCR signal strength is a key factor in deciding between two functionally distinct mature B cell compartments in the microenvironment of the spleen...

..Palindromic enhancers become demethylated later in B-cell differentiation, in B and plasma cells...

..The Immunological Genome Project combines immunology and computational biology laboratories in an effort to establish a complete 'road map' of gene-expression and regulatory networks in all immune cells...

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..The results of these studies will help to establish the types of selection that shape the expressed B cell repertoire, both fetally and in the adult, with implications for modulating normal and autoimmune responses. ..

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..The results of these studies will help to establish the types of selection that shape the expressed B cell repertoire, fetally and in the adult, with implications for modulating both normal and autoimmune responses. ..

..This work may eventually help us to understand the relationship of special features of fetal B cell development with autoreactivity nd B cell neoplasia...

..Specificities encoded by these V genes to be examined in detail will include both anti-thymocyte and anti-bromelain-treated mouse erythrocyte autoantibodies, both distinctively enriched in this population...

..Cumulatively, these studies will provide a clearer picture of fetal and adult B lymphopoiesis and distinguish whether the modes of selection affecting developing B cells are similar or different during these two ontogenic timi s. ..