Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca(2+) Influx in Nkx2-3 Knock-out Mice

B cells play a crucial role in the pathogenesis of rheumatoid arthritis. In Nkx2-3-deficient mice (Nkx2-3(−/−)) the spleen’s histological structure is fundamentally changed; therefore, B cell homeostasis is seriously disturbed. Based on this, we were curious, whether autoimmune arthritis could be induced in Nkx2-3(−/−) mice and how B cell activation and function were affected. We induced arthritis with immunization of recombinant human proteoglycan aggrecan G1 domain in Nkx2-3(−/−) and control BALB/c mice. We followed the clinical picture, characterized the radiological changes, the immune response, and intracellular Ca(2+) signaling of B cells. Incidence of the autoimmune arthritis was lower, and the disease severity was milder in Nkx2-3(−/−) mice than in control BALB/c mice. The radiological changes were in line with the clinical picture. In Nkx2-3(−/−) mice, we measured decreased antigen-induced proliferation and cytokine production in spleen cell cultures; in the sera, we found less anti-CCP-IgG2a, IL-17 and IFNγ, but more IL-1β, IL-4 and IL-6. B cells isolated from the lymph nodes of Nkx2-3(−/−) mice showed decreased intracellular Ca(2+) signaling compared to those isolated from BALB/c mice. Our findings show that the transcription factor Nkx2-3 might regulate the development of autoimmune arthritis most likely through modifying B cell activation.