Phosphorylation abnormalities: NZB mice exhibit a B-cell signalling defect

NZB mice demonstrate common and consistent abnormalities in B-cell activation and signalling. One of the hallmark characteristics of lupus disease is the prevalent hypergammaglobulinaemia, composed primarily of antinuclear antibodies. In addition to the hyperproliferation seen in mice exhibiting disease, the B cells also demonstrate a marked degree of hyperactivity in response to B-cell receptor occupancy. This points to an intrinsic defect in the signalling pathways regulating the response to an activation event. Correspondingly, B cells of NZB mice exhibit a significant lack of phosphatase activity, both at baseline and in response to stimulation. This is directly reflected by a higher level of phosphorylation of tyrosine residues. Individually, SAPK and SHIP-1, both players in the B-cell receptor signalling cascade, are also found to be abnormally phosphorylated in the NZB mouse. (C) 2002 Elsevier Science Ltd. All rights reserved.