Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease

Cell. 1995 Oct 20;83(2):301-11. doi: 10.1016/0092-8674(95)90171-x.


Mice homozygous for a disruption at the Lyn locus display abnormalities associated with the B lymphocyte lineage and in mast cell function. Despite reduced numbers of recirculating B lymphocytes, Lyn-/- mice are immunoglobulin M (IgM) hyperglobulinemic. Immune responses to T-independent and T-dependent antigens are affected. Lyn-/- mice fail to mediate an allergic response to IgE cross-linking, indicating that activation of LYN plays an indispensable role in Fc epsilon RI signaling. Lyn-/- mice have circulating autoreactive antibodies, and many show severe glomerulonephritis caused by the deposition of IgG immune complexes in the kidney, a pathology reminiscent of systemic lupus erythematosus. Collectively, these results implicate LYN as having an indispensable role in immunoglobulin-mediated signaling, particularly in establishing B cell tolerance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anaphylaxis / immunology
  • Animals
  • Antibody Formation
  • Autoimmune Diseases / etiology
  • Autoimmune Diseases / genetics*
  • B-Lymphocytes / pathology*
  • Base Sequence
  • Glomerulonephritis / genetics
  • Glomerulonephritis / immunology
  • Immune System / abnormalities*
  • Immunoglobulin E / immunology
  • Immunoglobulin M / blood
  • Kidney / pathology
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / immunology
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • src-Family Kinases / deficiency*
  • src-Family Kinases / genetics


  • Immunoglobulin M
  • Immunoglobulin E
  • src-Family Kinases