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 ˜3 weeks the number of B cells started to decline. While the combination of IL-10 and IL-4 was synerglstic 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 slgD⁺ B cells and slgD⁻ 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. Cytologlc 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.