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Interleukin-13 (IL-13) is a novel T-cell-derived cytokine with IL-4-like effects on many cell types. In human B lymphocytes, IL-13 induces activation, stimulates proliferation in combination with anti-IgM or anti-CD40 antibodies, and directs Ig isotype switching towards IgE and IgG4 isotypes. We show here that IL-13 also regulates human B-cell apoptosis. IL-13 reduced spontaneous apoptosis of peripheral blood B cells in vitro, as shown by measurement of DNA fragmentation using the TUNEL and Nicoletti assays. The inhibition of cell death by IL-13 alone was significant but modest, but was potently enhanced in combination with CD40 ligand (CD40L), a survival stimulus for B cells by itself. Interestingly, IL-13 increased the expression of CD40 on peripheral blood B cells, providing a possible mechanism for the observed synergy. IL-13 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 supraoptimal concentrations, which is consistent with the notion that the IL-4 and IL-13 binding sites share a common signaling subunit. The combination of IL-13 with CD40L augmented the expression of the Bcl-2 homologues Bcl-xL and Mcl-1, suggesting this as a possible intracellular mechanism of induced survival. By contrast, levels of Bcl-2, and two other Bcl-2 family members, Bax and Bak, remained unaltered. Given the importance of the CD40-CD40L interaction in B-cell responses, these results suggest a significant role of IL-13 in the regulation of B-cell apoptosis.

Type

Journal article

Journal

Blood

Publication Date

15/06/1997

Volume

89

Pages

4415 - 4424

Keywords

Apoptosis, B-Lymphocytes, CD40 Ligand, Cells, Cultured, Depression, Chemical, Drug Synergism, Gene Expression Regulation, Humans, Interleukin-13, Membrane Glycoproteins, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Recombinant Proteins, bcl-X Protein