Abstract
Dysregulated functions of B1 cells have been implicated in the disease progression of various autoimmune disorders, but it remains largely unclear whether B1 cells are involved in the pathogenesis of autoimmune arthritis. In this study, we found that peritoneal B1a cells underwent proliferation and migrated to the inflamed joint tissue with upregulated RANKL expression during collagen-induced arthritis (CIA) development in mice. Adoptive transfer of B1a cells exacerbated arthritic severity and joint damage while intraperitoneal depletion of B1 cells ameliorated both arthritic symptoms and joint pathology in CIA mice. In culture, RANKL-expressing B1a cells significantly promoted the expansion of osteoclasts derived from bone marrow cells, which were in accord with the in vivo findings of increased osteoclastogenesis in CIA mice transferred with B1a cells. Together, these results have demonstrated a pathogenic role of B1a cells in the development of autoimmune arthritis through RANKL-mediated osteoclastogenesis.
Highlights
Recent studies have identified the important contribution of conventional B (B2) cells to the development of autoimmune disease, but our current understanding for the role of B1 cells in autoimmune pathogenesis is still limited [1, 2]
To determine whether the increased number of B1a cells was due to proliferative expansion, carboxyfluorescein succinimidyl ester (CFSE) was injected into the peritoneal cavity (PC) of collagen II (CII)-immunized mice
We show that peritoneal B1a cells undergo proliferative expansion and migrate to peripheral lymphoid organs and inflamed joint tissue during the development of murine collagen-induced arthritis (CIA)
Summary
Recent studies have identified the important contribution of conventional B (B2) cells to the development of autoimmune disease, but our current understanding for the role of B1 cells in autoimmune pathogenesis is still limited [1, 2]. B1 cells have been recognized for their protective functions against viruses, bacteria and parasites by producing natural IgM antibodies [3], increasing evidence indicates that B1 cells, especially the highly polyspecific B1a cells, play a role in autoimmune pathogenesis [4]. Depletion of B1a cells by osmotic pressure ameliorates the development of type I diabetes [5], and reduces renal injury after kidney ischemia or reperfusion [9], indicating the involvement of B1a cells in disease progression. The frequency of these B1 cells is markedly elevated in SLE patients and correlated with disease pathogenesis and pathopersistence [13]
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