838 research outputs found
Developmental Regulation of B Lymphocyte Immune Tolerance Compartmentalizes Clonal Selection from Receptor Selection
AbstractB lymphocyte development is a highly ordered process that involves immunoglobulin gene rearrangements, antigen receptor expression, and a learning process that minimizes the development of cells with reactivity to self tissue. Two distinct mechanisms for immune tolerance have been defined that operate during early bone marrow stages of B cell development: apoptosis, which eliminates clones of cells, and receptor editing, which spares the cells but genetically reprograms their autoreactive antigen receptors through nested immunoglobulin L chain gene rearrangements. We show here that sensitivity to antigen-induced apoptosis arises relatively late in B cell development and is preceded by a functionally distinct developmental stage capable of receptor editing. This regulation compartmentalizes clonal selection from receptor selection
FcγRIIB1 Inhibition of BCR-Mediated Phosphoinositide Hydrolysis and Ca2+ Mobilization Is Integrated by CD19 Dephosphorylation
AbstractThe B cell receptor for immunoglobulin G, FcγRIIB1, is a potent transducer of signals that block antigen-induced B cell activation. Coligation of FcγRIIB1 with B lymphocyte antigen receptors (BCR) causes premature termination of phosphoinositide hydrolysis and Ca2+ mobilization and inhibits proliferation. This inhibitory signal is mediated in part by phosphorylation of FcγRIIB1 and recruitment of phosphatases; however, the molecular target(s) of effectors is unknown. Here we report that FcγRIIB1 inhibition of BCR signaling is mediated in part by selective dephosphorylation of CD19, a BCR accessory molecule and coreceptor. CD19 dephosphorylation leads to failed CD19 association with phosphatidylinositol 3-kinase, and this in turn leads to termination of inositol-1,4,5-trisphosphate production, intracellular Ca2+ release, and Ca2+ influx. The results define a molecular circuit by which FcγRIIB signals block phosphoinositide hydrolysis
Coupled modelling of plant uptake, soil water balance and soil solute transport for estimating the fate of cadmium and lead in amended agrosystems
Cyclopropane Modification of Trehalose Dimycolate Drives Granuloma Angiogenesis and Mycobacterial Growth through Vegf Signaling
Increased fibroblast proliferation induced by light emitting diode and low power laser irradiation
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