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• W2023126373 abstract "The ability of immune complexes (IC) to regulate B lymphocyte differentiation was investigated. Using an in vitro model, we previously demonstrated that macrophages (M phi) or lymphoid dendritic cells pulsed with IC differentially regulated B cell function, inducing unresponsiveness or stimulation, respectively. The capacity of M phi to induce unresponsiveness was dependent upon two signals, an antigen-specific one supplied by the IC and M phi-secreted prostaglandin (PG)E2. Total inhibition of antibody production was never achieved as a small percentage of B lymphocytes were resistant to IC-induced unresponsiveness. In this study, utilizing an accessory cell-free system, we demonstrate that splenic B cell fractions separated on Percoll density gradients are heterogeneous in their sensitivity to IC-mediated unresponsiveness. Small resting B lymphocytes are exquisitely sensitive to IC-mediated negative signaling and exhibit virtual total ablation of antibody responses. Conversely, large activated B cells are more refractory to this inhibitory pathway. PGE2 and other agents which elevate cAMP potentiate IC-induced unresponsiveness in resting, but not activated B lymphocytes. In addition treatment of resting B cells with PGF2 alpha, which did not elevate cAMP, failed to sensitize these cells to IC-mediated negative signaling. Unresponsiveness induced by IC is selective for specific aspects of B lymphocyte activation, since B cell differentiation but not proliferation is affected. Furthermore, pre-treatment of resting B lymphocytes with interleukin 4 prevents the IC-induced ablation of IgM antibody responses. Overall, our results indicate that the binding of IC by resting B lymphocytes provides a potent mechanism for inhibiting differentiation without affecting proliferation. These observations suggest that in vivo, IC play an important role in regulating the memory B lymphocyte pathway." @default.
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• W2023126373 date "1991-02-01" @default.
• W2023126373 modified "2023-09-27" @default.
• W2023126373 title "Elevated levels of intracellular cAMP sensitize resting B lymphocytes to immune complex-induced unresponsiveness" @default.
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• W2023126373 doi "https://doi.org/10.1002/eji.1830210211" @default.
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