Recombinant interleukin 2 or 5, but not 3 or 4, induces maturation of resting mouse B lymphocytes and propagates proliferation of activated B cell blasts

Abstract

Plasmacytoma transformants of the X63-Ag8-653 cell line carrying an expression vector with either IL-2, -3, -4, or -5 cDNA were established that secrete the corresponding ILs at high rates. The four mouse ILs (mILs) were then tested as single ILs and in combinations for their effects on the maturation of resting and proliferation of activated normal mouse splenic B cells. mIL-3 and mIL-4 were inactive in all assays. mIL-2, as well as mIL-5, synergized with Ig-specific antibodies and B cell growth factor alpha (BCGF-alpha) to stimulate successive rounds of B cell division with LPS-activated B cells. This activity as BCGF-beta was effective at concentrations similar to those at which mIL-2 induced proliferation of the CTL-L T cell line, indicating a high-affinity interaction of both mIL-2 and mIL-5 with their corresponding receptors on activated B cells. mIL-5 and maybe IL-2 also induced maturation of resting B cells to Ig-secreting cells without proliferation. This B cell maturation factor (BMF) activity of mIL-5 was as effective as its BCGF-beta activity, while the BMF activity of mIL-2 was at least 10(2)-fold less effective. BMF activity of mIL-2, but not mIL-5, was blocked by anti-Il-2-R antibodies, indicating that mIL-2 and mIL-5 use separate receptors for B cell signaling. mIL-2, as well as mIL-5, furthermore, acted as filler activities when proliferation in the presence of Ig-specific antibodies and BCGF-alpha was measured with as little as 500 B cells. In the case of mIL-5, this was also true for maturation of that few cells. Limiting dilution analyses showed that approximately 1-2% of the resting B cells matured without division, while 30-100-fold fewer cells (0.03-0.06%) proliferated and matured in response to IL-5. A single IL, therefore, is capable of inducing maturation and of stimulating mitotic cell cycle progression of normal B cells.