B-cell anergy is maintained in anti-DNA transgenic NZB/NZW mice

• Published in: International immunology Vol. 22; no. 2; pp. 101 - 111
• Main Authors: Kat, Inbal, Makdasi, Efi, Fischel, Ruth, Eilat, Dan
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.02.2010
• Subjects: Animals; Antibodies, Antinuclear - blood; autoimmunity; Autoimmunity - genetics; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Calcium - metabolism; Cells, Cultured; Clonal Anergy - genetics; Disease Models, Animal; lupus; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - metabolism; Lymphocyte Activation; Mice; Mice, Inbred NZB; Mice, Transgenic; Receptors, Antigen, B-Cell - immunology; Spleen - immunology; Spleen - metabolism; tolerance; Toll-Like Receptor 9 - immunology; transitional B cells; autoimmunity; transitional B cells; lupus; tolerance
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxp120

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.