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Follicular dendritic cells (FDCs), the best defined stromal cell subset within lymphoid follicles, play a critical role in presenting intact antigen to B lymphocytes. The discovery that many follicular stromal cells make B-lymphocyte chemoattractant (BLC), a CXC chemokine that attracts CXCR5+ cells, provides a basis for understanding how motile B cells come(More)
B lymphocytes re-circulate between B-cell-rich compartments (follicles or B zones) in secondary lymphoid organs, surveying for antigen. After antigen binding, B cells move to the boundary of B and T zones to interact with T-helper cells. Despite the importance of B--T-cell interactions for the induction of antibody responses, the mechanism causing B-cell(More)
Immunoglobulin family tyrosine-based activation motifs (ITAM), which define the conserved signaling sequence EX2YX2L/IX7YX2L/I, couple the T cell antigen receptor (TCR) to cellular proteins including protein tyrosine kinases (PTK) and adapter molecules. The TCR is a multichain complex with four invariant chains CD3 gamma, delta and epsilon that each contain(More)
Bruton's tyrosine kinase (Btk) is a therapeutic target for rheumatoid arthritis, but the cellular and molecular mechanisms by which Btk mediates inflammation are poorly understood. Here we describe the discovery of CGI1746, a small-molecule Btk inhibitor chemotype with a new binding mode that stabilizes an inactive nonphosphorylated enzyme conformation.(More)
Despite the established role for PI3Ks in cell migration, the PI3Ks involved in lymphocyte chemotaxis are poorly defined. In this study, we report that p110gamma-deficient T cells, but not B cells, show reduced chemotactic responses to the lymphoid chemokines, CCL19, CCL21, and CXCL12. As B cell and T cell chemotactic responses were both sensitive to the(More)
T and B lymphocytes migrate hundreds of micrometers each day to survey the body's lymphoid tissues for antigens. No other mammalian cell type undergoes such extensive and continual movement, raising the question of whether lymphocytes have specializations to support their migratory behavior. This possibility has recently gained support from studies of mice(More)
To assess the effects and mechanisms of a CD200R1 agonist administered during the progressive stage of a multiple sclerosis model, we administered CD200R1 agonist (CD200Fc) or control IgG2a during the chronic phase of disease (days 10-30) in mice with experimental autoimmune encephalomyelitis (EAE), induced using myelin oligodendrocyte glycoprotein peptide(More)
Ag-mediated changes in B lymphocyte migration are important for normal immune function, yet the mechanisms by which these changes occur are poorly defined. Because chemokines direct many lymphocyte movements, molecules that regulate signaling by G protein-coupled chemokine receptors are likely to participate in Ag receptor-induced changes in cell migration.(More)
The delivery of signals that control the growth of T cells is a key event for effective co-ordination of T-cell-dependent immune responses. It is now recognized that guanine nucleotide binding proteins play an important role in signal transduction by the T-cell receptor (TCR) and cytokine receptors. Here, Manolo Izquierdo Pastor, Karin Reif and Doreen(More)
Cell cycle progression initiated by interleukin-2 (IL-2) in T cells is critical for lymphoproliferation and an immune response. Phosphatidyl inositol 3-kinase (PI3K) is activated by IL-2. However, nuclear targets for PI3K are not known. Here we identify the cell cycle regulator E2F as an IL-2 target in T lymphocytes and PI3K as the critical signaling(More)