An imbalance between serine and tyrosine phosphatases in systemic lupus erythematosus (SLE) contributes to an intrinsically disturbed balance of B-cell receptor (BCR) initiated signaling pathways, resulting in enhanced survival of lupus B-cells and differentiation into plasma cells. This according to a study of B-cells from healthy donors (HDs) and patients with SLE. Researchers found:

• B-cells from patients with SLE showed diminished Syk phosphorylation and reduced intracellular calcium release after BCR activation vs HDs.

• This was related to enhanced activity of tyrosine but not serine/threonine phosphatases and was corrected by inhibition of tyrosine phosphatase activity.

• In contrast to reduced Syk phosphorylation after BCR activation, phosphorylation of Akt was significantly increased in SLE B-cells.

• The disturbed balance between Syk and Akt phosphorylation was significantly correlated with B-cell survival following BCR engagement.

• CD27-, but not CD27+, B-cells of patients with SLE showed increased expression and phosphorylation of the inhibitory BCR coreceptor CD22.

Citation: Fleischer SJ, Daridon C, Fleischer V, Lipsky PE, Dӧrner T. Enhanced tyrosine phosphatase activity underlies dysregulated B-cell receptor signaling and promotes survival of human lupus B-cells. [Published online ahead of print December 29, 2015]. Arthritis Rheumatol. doi: 10.1002/art.39559.