Multiple defects in the immune system of Lyn-deficient mice, culminating in autoimmune disease
ML Hibbs, DM Tarlinton, J Armes, D Grail, G Hodgson… - Cell, 1995 - cell.com
Cell, 1995•cell.com
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 FceRl signaling. LynP mice have circulating autoreactive antibodies …
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 FceRl signaling. LynP mice have circulating autoreactive antibodies …
Summary
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 FceRl signaling. LynP 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.
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