INTERLEUKIN-13 IN COMBINATION WITH CD40 LIGAND POTENTLY INHIBITS APOPTOSIS IN HUMAN B-LYMPHOCYTES - UP-REGULATION OF BCL-XL AND MCL-1

Interleukin-13 (IL-13) is a novel T-cell-derived cytokine with IL-4-li ke effects on many cell types. In human B lymphocytes, IL-13 induces a ctivation, stimulates proliferation in combination with anti-IgM or an ti-CD40 antibodies, and directs Ig isotype switching towards IgE and I gG4 isotypes. We show here that IL-13 also regulates human B-cell apop tosis. IL-13 reduced spontaneous apoptosis of peripheral blood B cells in vitro, as shown by measurement of DNA fragmentation using the TUNE L and Nicoletti assays. The inhibition of cell death by IL-13 alone wa s significant but modest, but was potently enhanced in combination wit h CD40 ligand (CD40L), a survival stimulus for B cells by itself. Inte restingly, IL-13 increased the expression of CD40 on peripheral blood B cells, providing a possible mechanism for the observed synergy. IL-1 3 alone was a less potent inhibitor of apoptosis than IL-4. Moreover, there was no additive effect of combining IL-4 and IL-13 at supraoptim al concentrations, which is consistent with the notion that the IL-4 a nd IL-13 binding sites share a common signaling subunit. The combinati on of IL-13 with CD40L augmented the expression of the Bcl-2 homologue s Bcl-xL and Mcl-1, suggesting this as a possible intracellular mechan ism of induced survival. By contrast, levels of Bcl-2, and two other B cl-2 family members, Bar and Bak, remained unaltered. Given the import ance of the CD40-CD40L interaction in B-cell responses, these results suggest a significant role of IL-13 in the regulation of B-cell apopto sis. (C) 1997 by The American Society of Hematology.