Regulation of B-1 cell activation and its autoantibody production by Lyn kinase-regulated signallings

The src-family protein tyrosine kinase, Lyn, has been reported to play a cr ucial role in the regulation of B-cell antigen receptor (BCR)-mediated sign alling. To elucidate the role of Lyn in the maintenance of immunological to lerance and the prevention of B-1 cell activation and its autoantibody prod uction, Lyn-deficient mice were crossed with transgenic mice carrying the i mmunoglobulin heavy and light chain genes encoding an autoantibody against mouse red blood cells. In the transgenic mice, most peripheral B cells expr essed the B-1 cell phenotype. When the transgenic mice were bred in specifi c pathogen-free (SPF) conditions, B-1 cells were anergic and did not produc e any autoantibody. In contrast, Lyn-deficient transgenic mice kept in the same SPF conditions revealed markedly increased numbers of activated B-1 ce lls and developed severe autoimmune haemolytic anaemia. Moreover, the mice had a huge splenomegaly containing a remarkable accumulation of erythroblas ts, resulted from extramedullary erythropoiesis, in addition to the increas ed numbers of lymphoblast-like cells of the B-1 cell lineages. The present study demonstrates a crucial role of Lyn kinase in the regulation of B-1 ce ll activation and maintenance of tolerance.