OBJECTIVE: @entity1252 ( @entity1252 ) is associated with hyperactivity of B cells and abnormalities of B cell receptor (BCR) signaling. To address the linkage between dysregulated BCR signaling and increased B cell function, we assessed immediate phosphorylation events in lupus B cells. METHODS: B cells from @entity1252 @entity1 and healthy donors were analyzed by flow cytometry to assess phosphorylated @entity10317 , @entity10255 , and Akt as well as the basal expression of the BCR coreceptors @entity10317 and @entity1075 . Confocal microscopy studies determined the recruitment of @entity10317 and the @entity4149 phosphatase SH2 domain-containing phosphatase 1 to the activated BCR complex. Additionally, phosphatase activity in @entity1252 versus healthy donor B cells was measured. RESULTS: B cells from @entity1252 @entity1 showed diminished @entity10255 phosphorylation and reduced intracellular @entity460 release after BCR activation as compared to B cells from healthy donors. This was related to an enhanced activity of @entity4149 , but not @entity563 / @entity1889 , phosphatases and was corrected by inhibition of @entity4149 phosphatase activity. In contrast to reduced @entity10255 phosphorylation after BCR activation, phosphorylation of Akt was significantly increased in @entity1252 B cells. The disturbed balance between @entity10255 and Akt phosphorylation was significantly correlated with B cell survival following BCR engagement. Furthermore, @entity2731 -, but not @entity2731 +, B cells from @entity1252 @entity1 displayed increased expression and phosphorylation of the inhibitory BCR coreceptor @entity10317 . CONCLUSION: These results indicate that an imbalance between @entity563 and @entity4149 phosphatases in @entity1252 contributes to an intrinsically disturbed balance of BCR-initiated signaling pathways, resulting in enhanced survival of lupus B cells and differentiation into plasma cells.

Enhanced XXXX Phosphatase Activity Underlies Dysregulated B Cell Receptor Signaling and Promotes Survival of @entity1 Lupus B Cells.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity1075 :: ('930', 'Gene') :: ['CD19'] @entity2731 :: ('939', 'Gene') :: ['CD27'] @entity1252 :: ('MESH:D008180', 'Disease') :: ['SLE', 'Systemic lupus erythematosus'] @entity10255 :: ('6850', 'Gene') :: ['Syk'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity563 :: ('CHEBI:17822', 'Chemical') :: ['serine'] @entity1889 :: ('CHEBI:26986', 'Chemical') :: ['threonine'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine'] @entity10317 :: ('933', 'Gene') :: ['CD22']
@entity4149 :: (D014443,Chemical) :: ['Tyrosine']
