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

• Published in: Immunology 1999-12, Vol.98 (4), p.595-603
• Main Authors: Ochi, H., Takeshita, H., Suda, T., Nisitani, S., Honjo, T., Watanabe, T.
• Format: Article
• Language: English
• Subjects: AB-1 cells; AB-cell receptor; Anemia, Hemolytic, Autoimmune - immunology; Animals; Antibody-Producing Cells - immunology; Autoantibodies - immunology; B-Lymphocytes - immunology; Erythrocytes - immunology; Lymphocyte Activation; Lyn protein; Mice; Mice, Inbred C57BL; Mice, Transgenic; Original; Specific Pathogen-Free Organisms; Spleen - immunology; src-Family Kinases - immunology
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1046/j.1365-2567.1999.00899.x

Summary 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.