B-1 lymphocytes differentiate into functional osteoclast-like cells

Abstract

The existence of murine peritoneal osteoclast precursors has been already described. Also, recent reports evidenced an interplay between B lymphocytes and osteoclasts development. B-1 cells comprise a B-lymphocyte subset that resides mostly in pleural and peritoneal cavities. It has been demonstrated that B-1 cells can differentiate into mononuclear phagocytes and form multinucleated giant cells. Based on these findings, we investigated the role of B-1 lymphocytes in bone resorption and osteoclastogenesis. In vivo experimental periodontitis induced in B-1 deficient Xid mice demonstrated that bone resorption is impaired in these animals. However, reconstitution of Xid mice with B-1 cells increased bone resorption to near Balb/c values. B-1 cell derived phagocytes express the receptor activator of nuclear factor-κB (RANK) and the macrophage colony-stimulating factor receptor (M-CSFR). When cultured with RANK-ligand (RANKL) and M-CSF, B-1 cells became tartrate resistant acid phosphatase (TRAP) positive multinucleated cells, a typical osteoclast phenotype. Lacunae formation was observed when cells were cultivated onto a calcium phosphate analog, indicating functional differentiation of B1 cells into osteoclast-like cells. The dynamics of their IgM expression showed that this lymphoid marker was downregulated along the differentiation of B-1 lymphocytes into osteoclasts. Our results unveiled the first evidence that B-1 cells have a role in osteoclastogenesis and bone resorption and offer new insights in the relationship between bone and lymphoid cells.