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 of B lympho cytes triggered through their CD40. During the initial phase, IL-10 wa s as potent as IL-4 in inducing the expansion of viable B cells. Then, cellular expansion slowed down and after similar to 3 weeks the numbe r 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 recover y declined after 3 weeks, indicating that IL-10 prevails over IL-4. Th ose effects were not restricted to a specific B cell subset as both sl gD(+) B cells and slgD(-) B cells behaved in a similar way, though the latter population responded with a slightly accelerated kinetic, Inve rted microscope examination and scanning electron microscopy showed th at in response to IL-10, CD40-activated B cell cultures were heterogen eous with loose aggregates of cells as well as free floating large ovo id cells. In contrast, in the presence of IL-4, CD40-activated B cell cultures were essentially composed of tight cell clumps, IL-10 progres sively induced all B cells to differentiate into non-replicating cells with intracytoplasmic ig that secreted Ig at a high rate. Cytologic a nalysis indicated that IL-10 cultured cells display a basophilic cytop lasm with an arcoplasm and a low nucleus/cytoplasm ratio. Transmission electron microscopy demonstrated that when IL-10 was added to the cul ture, B cells displayed structures for excretion with extended endopla smic reticulum and dilated cisternae containing paracrystalline struct ures, typical of plasmablasts cells. Taken together, these results ind icate that IL-10 acts as a plasma cell differentiation factor for CD40 -activated B cells.