Fig. 7: B-cell responses were inhibited by DHODH inhibitor (Orludodstat) comparable to DSF and can be restored by Uridine, but not DSF. | Communications Biology

Fig. 7: B-cell responses were inhibited by DHODH inhibitor (Orludodstat) comparable to DSF and can be restored by Uridine, but not DSF.

From: Disulfiram treatment suppresses antibody-producing reactions by inhibiting macrophage activation and B cell pyrimidine metabolism

Fig. 7

a B-cell cluster formation after stimulation with IL-4 plus anti-CD40 antibody or LPS with or without pre-treatment with indicated concentrations of Orludodstat. Numbers of B cells (b) and CD138+ plasma cells (c) recovered after 4-day culture in the presence of indicated concentrations of Orludodstat, stimulated by IL-4 plus anti-CD40 (upper panel) or LPS (lower panel), and effect of uridine added to the B cell culture on the inhibitory effect of Orludodstat (NC, unstimulated, n = 6; IL4+anti-CD40, n = 6; LPS, n = 6; stimulated in the presence of Orludodstat, n = 3 biologically independent samples). d Simplified schematic of pyrimidine synthesis in de novo synthesis and salvage pathways. Effect of uridine added to the B-cell culture on the inhibitory effect of DSF on B cells (e) and CD138+ plasma cells (f) recovered after stimulation with IL4+anti-CD40 (upper panel) or LPS (lower panel) (NC, unstimulated, n = 6; IL4 + aCD40, n = 6; LPS, n = 6; stimulated in the presence of DSF, n = 3 biologically independent samples). DSF decreased the salvage pathway-driven B cell response induced by inhibition of the de novo pathway by the DHODH inhibitor and addition of uridine in B220+ cells (g) or CD138+ plasma cells (h) (n = 3 biologically independent samples). Significance was calculated using one-way ANOVA with Tukey’s post-hoc test: *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Data are shown as the mean ± SEM. d was generated using Servier Medical Art, licensed under a Creative Commons Attribution 3.0 Unported License.

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