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

We compared the effects of IL-10 and IL-4 on the functions ofB lymphocytes triggered through their CD40. During the initialphase, IL-10 was as potent as IL-4 in inducing the expansionof viable B cells. Then, cellular expansion slowed down andafter {small tilde}3 weeks the number of B cells started todecline. While the combination of IL-10 and IL-4 was synerglsticduring the first 2 weeks of culture, B cell recovery declinedafter 3 weeks, indicating that IL-10 prevails over IL-4. Thoseeffects were not restricted to a specific B cell subset as bothslgD⁺ B cells and slgD^– B cells behaved in a similar way,though the latter population responded with a slightly acceleratedkinetic. Inverted microscope examination and scanning electronmicroscopy showed that in response to IL-10, CD40-activatedB cell cultures were heterogeneous with loose aggregates ofcells as well as free floating large ovoid cells. In contrast,in the presence of IL-4, CD40-activated B cell cultures wereessentially composed of tight cell clumps. IL-10 progressivelyinduced all B cells to differentiate into non-replicating cellswith intracytoplasmic Ig that secreted Ig at a high rate. Cytologlcanalysis indicated that IL-10 cultured cells display a basophiliccytoplasm with an arcoplasm and a low nucleus/cytoplasm ratio.Transmission electron microscopy demonstrated that when IL-10was added to the culture, B cells displayed structures for excretionwith extended endoplasmic reticulum and dilated cisternae containingparacrystalline structures, typical of plasmablasts cells. Takentogether, these results indicate that IL-10 acts as a plasmacell differentiation factor for CD40-activated B cells.