Terminal differentiation of spontaneous rheumatoid factor–secreting B cells from rheumatoid arthritis patients depends on endogenous interleukin‐1 0

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Abstract
Objective. The presence of serum rheumatoid factor (RF) and spontaneous RF-secreting B cells is a common feature in most patients with rheumatoid arthritis (RA). This study analyzed the cytokine(s) that controls the final maturation of B cells capable of spontaneous IgM-RF secretion in vitro. Methods. RA patients' peripheral blood mononuclear cells (PBMC), as well as adherent and nonadherent cell fractions, were cultured, and spontaneous IgM-RF and interleukin-1 0 (IL-1 0) secretion were determined by enzyme-linked immunosorbent assay. Results. The RF+ RA PBMC, but not PBMC from RF– RA patients or healthy controls, actively produced IgM-RF in a linear manner for 14 days. This activity depended on the presence of fetal calf serum and did not require cellular DNA synthesis. Spontaneous IgM-RF secretion depended on IL-1 0, as deduced from the following findings: 1) IL-1 0, but not a variety of cytokines including IL-6, restored missing IgM-RF secretion by PBMC in serum-free supplemented cultures; 2) the addition of anti–IL-1 0, but not anti–IL-6, blocking antibodies inhibited PBMC IgM-RF secretion, and this effect could be reversed by exogenous IL-1 0; and 3) RA PBMC actively produced IL-1 0 in vitro. The cells responsible for endogenous IL-1 0 production were found in the adherent cell fraction. Finally, IL-1 0 induced IgM-RF, but not total IgM, secretion by RA PBMC. Conclusion. In patients with RA, circulating B cells capable of spontaneous IgM-RF secretion require IL-1 0 production by adherent cells to reach terminal maturation.