Mouse IL-13 Enhances Antibody Production In Vivo and Acts Directly on B Cells In Vitro to Increase Survival and Hence Antibody Production

Abstract

IL-13, a Th2 cytokine, exhibits similar functions to IL-4 in stimulating proliferation and class switching of human B cells. Although mouse B cells were reported to be unresponsive to IL-13, we now show that IL-13 directly stimulates mouse B cells, causing extended survival and higher Ab levels. Recombinant mouse IL-13 was administered via osmotic pump during immunization of BALB/c mice with chicken RBCs. IL-13 treatment enhanced not only the plasma levels of total IgG1, IgG2a, and IgG2b but also Ag-specific Ig levels. To examine whether IL-13 acted directly on mouse B cells, B220+ B cells were cultured with fixed, anti-CD3-activated Th2 clones. Production of IgM and IgG1 was enhanced moderately by IL-13 and strongly by IL-4. Anti-CD40-stimulated sIgD+ mouse B cells also responded to IL-13 by producing increased levels of IgM, and to a lesser extent IgG1, IgG2a, IgG2b, and IgG3. No evidence was found for IL-13-induced class switching. Mouse B cells were stimulated directly rather than indirectly via contaminating cells, as IL-13 increased the numbers of both total and Ab-secreting B cells in aliquots of 100 sIgD+ B cells (>99.5% pure) stimulated with anti-CD40 Ab. Stimulation of B cells by IL-13 was unaffected by the addition of anti-IL-4 to the cultures. In contrast to IL-4, IL-13 did not increase CD23 expression or B cell proliferation as measured by dilution of an intracellular fluorescence label. Collectively, these data indicate that IL-13 can enhance mouse B cell Ab production by increasing survival of the B cells.