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

H. Ochi, H. Takeshita, T. Suda, S. Nisitani, T. Honjo, T. Watanabe

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)595-603
Number of pages9
JournalImmunology
Volume98
Issue number4
DOIs
Publication statusPublished - 1999

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Autoantibodies
Phosphotransferases
Transgenic Mice
Specific Pathogen-Free Organisms
src-Family Kinases
Immunoglobulin Light Chain Genes
Maintenance
Immunoglobulin Heavy Chain Genes
Autoimmune Hemolytic Anemia
Erythroblasts
B-Cell Antigen Receptors
Erythropoiesis
Splenomegaly
Cell Lineage
B-Lymphocytes
Erythrocytes
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Regulation of B-1 cell activation and its autoantibody production by Lyn kinase-regulated signallings. / Ochi, H.; Takeshita, H.; Suda, T.; Nisitani, S.; Honjo, T.; Watanabe, T.

In: Immunology, Vol. 98, No. 4, 1999, p. 595-603.

Research output: Contribution to journalArticle

Ochi, H, Takeshita, H, Suda, T, Nisitani, S, Honjo, T & Watanabe, T 1999, 'Regulation of B-1 cell activation and its autoantibody production by Lyn kinase-regulated signallings', Immunology, vol. 98, no. 4, pp. 595-603. https://doi.org/10.1046/j.1365-2567.1999.00899.x
Ochi, H. ; Takeshita, H. ; Suda, T. ; Nisitani, S. ; Honjo, T. ; Watanabe, T. / Regulation of B-1 cell activation and its autoantibody production by Lyn kinase-regulated signallings. In: Immunology. 1999 ; Vol. 98, No. 4. pp. 595-603.
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