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

17 Citations (Scopus)

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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