Monocytosis and accelerated activation of lymphocytes in C1q-deficient autoimmune-prone mice.
C1q deficiency has been shown to accelerate spontaneous autoimmunity in mice. We studied the time course of activation of monocytes and lymphocytes in autoimmune and non-autoimmune mice in the presence or absence of C1q as a disease accelerator. Autoimmune MRL\Mp.C1qa-\- and non-autoimmune C57BL\6.C1qa-\- mice were analysed at various time points between 6 and 33 weeks of age and compared to strain- and age-matched C1q-sufficient controls. Splenic and peritoneal leucocytes were analysed by flow cytometry and plasma levels of immunoglobulin M (IgM), total IgG, IgG subclasses and IgM autoantibodies were measured. Both C1q-deficient strains had significantly more splenic monocytes than their controls at all time points analysed. In addition, MRL\Mp.C1qa-\- but not C57BL/6.C1qa-\- mice developed splenic hypercellularity starting at about 12-17 weeks old, had signs of accelerated CD4+ T-cell activation and showed a marked increase in splenic plasma cells and total serum IgM levels from about 22 weeks of age. The accelerated CD4+ T-cell activation was not due to a direct inhibitory effect of C1q on T cells. These data show that C1q deficiency causes splenic monocytosis together with accelerated T-cell activation in an autoimmune-prone mouse strain.
Rheumatology Section, Eric Bywaters Centre, Faculty of Medicine, Imperial College, Hammersmith Campus, London, UK.
Marten
M
Trendelenburg
Anthony P
AP
Manderson
Liliane
L
Fossati-Jimack
Mark J
MJ
Walport
Marina
M
Botto
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D015922:Complement C1q / Q000172:deficiency*; D005260:Female; D020022:Genetic Predisposition to Disease; D007075:Immunoglobulin M / Q000097:blood; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D013154:Spleen / Q000276:immunology
D007075:Immunoglobulin M; D015922:Complement C1q