Long-term cultured CD40-activated B lymphocytes differentiate into plasma cells in response to IL-10 but not IL-4

Abstract

We compared the effects of IL-10 and IL-4 on the functions of B lymphocytes triggered through their CD40. During the initial phase, IL-10 was as potent as IL-4 in inducing the expansion of viable B cells. Then, cellular expansion slowed down and after approximately 3 weeks the number of B cells started to decline. While the combination of IL-10 and IL-4 was synergistic during the first 2 weeks of culture, B cell recovery declined after 3 weeks, indicating that IL-10 prevails over IL-4. Those effects were not restricted to a specific B cell subset as both sIgD+ B cells and sIgD- B cells behaved in a similar way, though the latter population responded with a slightly accelerated kinetic. Inverted microscope examination and scanning electron microscopy showed that in response to IL-10, CD40-activated B cell cultures were heterogeneous with loose aggregates of cells as well as free floating large ovoid cells. In contrast, in the presence of IL-4, CD40-activated B cell cultures were essentially composed of tight cell clumps. IL-10 progressively induced all B cells to differentiate into non-replicating cells with intracytoplasmic Ig that secreted Ig at a high rate. Cytologic analysis indicated that IL-10 cultured cells display a basophilic cytoplasm with an arcoplasm and a low nucleus/cytoplasm ratio. Transmission electron microscopy demonstrated that when IL-10 was added to the culture, B cells displayed structures for excretion with extended endoplasmic reticulum and dilated cisternae containing paracrystalline structures, typical of plasmablasts cells. Taken together, these results indicate that IL-10 acts as a plasma cell differentiation factor for CD40-activated B cells.

Epstein–Barr virus can inhibit genotoxin-induced G1 arrest downstream of p53 by preventing the inactivation of CDK2

“…Subsequently it was reported that, although IL10 could induce CD40-activated B cells to differentiate into plasma cells, IL4 did not have this effect (Rousset et al, 1995). Using this system with murine fibroblasts expressing CD40L (CD154) in combination with recombinant IL4 (Figure 1a), we have consistently found that CD19-positive peripheral human B cells actively proliferate in culture for only 3-4 weeks before arresting and showing signs of terminal differentiation (manuscript in preparation).…”

The Expression of p18INK4 and p27kip1 Cyclin-Dependent Kinase Inhibitors Is Regulated Differently During Human B Cell Differentiation

“…For instance, after stimulation with the combination of the B cell mitogen SAC, IL-2, and IL-10, accumulation of activated cells in G 1 and subsequent Ig secretion take place after a single round of proliferation, whereas G 1 arrest and Ig secretion observed after activation with CD40 and IL-10 occur after several rounds of proliferation, leading to quantifiable cell growth ( Fig. 6B) (40,41). Hasbold et al reported that after CD40 and IL-4 stimulation of murine B cells, IgG secretion was observed after three rounds of proliferation, whereas IgE production was only evidenced after five proliferative rounds (42).…”

Increased Frequency of Pre-germinal Center B Cells and Plasma Cell Precursors in the Blood of Children with Systemic Lupus Erythematosus

“…This suggests that they are the products of a recent clonal expansion that probably occurred in a GC, given the presence of unique mutations. This expansion may be explained by increased IL-10, a major plasma cell differentiation factor (56). Indeed, high levels of IL-10 are found in the serum of SLE patients, and treatment of these patients with anti-IL-10 Abs has shown beneficial effects (57-59).…”