B-cell anergy is maintained in anti-DNA transgenic NZB/NZW mice.
Clonal anergy has been well recognized as an important mechanism of B cell immunologic tolerance. However, the properties of anergic B cells and especially their role in the development of autoimmune disease in susceptible animals have been controversial. Here we show that low-affinity anti-DNA anergic B cells populate the mature B-cell compartment in the mouse spleen in excessive numbers and display paradoxical behavior in response to a combined B-cell receptor/TLR9 activation. Surprisingly, B-cell anergy was maintained in aged NZB/NZW F1 mice that develop a systemic lupus erythematosus (SLE)-like autoimmune disease. In several parameters of anergy, such as calcium mobilization and antibody secretion, the lupus-prone mice appeared more anergic than their non-autoimmune counterparts. We conclude that low-affinity anergic B cells are unlikely to serve as precursors for the high-affinity autoreactive B cells that give rise to pathogenic anti-DNA auto-antibodies in SLE.
Kat
Inbal
I
Department of Medicine, Hadassah University Hospital, The Hebrew University Faculty of Medicine, Jerusalem 91120, Israel.
Makdasi
Efi
E
Fischel
Ruth
R
Eilat
Dan
D
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood*; D015551:Autoimmunity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D017635:Clonal Anergy / Q000235:genetics; D004195:Disease Models, Animal; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008814:Mice, Inbred NZB; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D013154:Spleen / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000276:immunology
D000974:Antibodies, Antinuclear; D011947:Receptors, Antigen, B-Cell; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D002118:Calcium