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 crucial role in the regulation of B-cell antigen receptor (BCR)-mediated signalling. To elucidate the role of Lyn in the maintenance of immunological tolerance and the prevention of B-1 cell activation and its autoantibody production, Lyn-deficient mice were crossed with transgenic mice carrying the immunoglobulin heavy and light chain genes encoding an autoantibody against mouse red blood cells. In the transgenic mice, most peripheral B cells expressed the B-1 cell phenotype. When the transgenic mice were bred in specific pathogen-free (SPF) conditions, B-1 cells were anergic and did not produce any autoantibody. In contrast, Lyn-deficient transgenic mice kept in the same SPF conditions revealed markedly increased numbers of activated B-1 cells and developed severe autoimmune haemolytic anaemia. Moreover, the mice had a huge splenomegaly containing a remarkable accumulation of erythroblasts, resulted from extramedullary erythropoiesis, in addition to the increased 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 cell activation and maintenance of tolerance.
Ochi
H
H
Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Takeshita
H
H
Suda
T
T
Nisitani
S
S
Honjo
T
T
Watanabe
T
T
D000744:Anemia, Hemolytic, Autoimmune / Q000276:immunology*; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D004912:Erythrocytes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology; D019061:src-Family Kinases / Q000276:immunology*
D001323:Autoantibodies; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases