*Article* **Ameliorated Autoimmune Arthritis and Impaired B Cell Receptor-Mediated Ca2**<sup>+</sup> **Influx in Nkx2-3 Knock-out Mice**

**Esam Khanfar 1, Katalin Olasz 1, Fanni Gábris 1,2, Erzsébet Gajdócsi 1, Bálint Botz 3,4, Tamás Kiss 4,5, Réka Kugyelka 1, Tímea Berki 1, Péter Balogh 1,2 and Ferenc Boldizsár 1,\***


Received: 23 July 2020; Accepted: 25 August 2020; Published: 26 August 2020

**Abstract:** 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−/<sup>−</sup> 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−/<sup>−</sup> and control BALB/c mice. We followed the clinical picture, characterized the radiological changes, the immune response, and intracellular Ca2<sup>+</sup> signaling of B cells. Incidence of the autoimmune arthritis was lower, and the disease severity was milder in Nkx2-3−/<sup>−</sup> mice than in control BALB/c mice. The radiological changes were in line with the clinical picture. In Nkx2-3−/<sup>−</sup> 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−/<sup>−</sup> mice showed decreased intracellular Ca2<sup>+</sup> 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.

**Keywords:** autoimmune arthritis; Nkx2-3; B cell activation
