Interleukin-11 promotes accessory cell-dependent B-cell differentiation in humans

Interleukin-11 (IL-11) is a recently described stromal-derived cytokine that supports the growth of an IL-6-dependent murine plasmacytoma line in the presence of antibody to IL-6 and appears to act in a manner similar to IL-6 on hematopoietic stem cells. Because IL-6 is known to promote differentiation of normal human B cells, the role of IL-11 on B-cell differentiation in vitro was characterized. IL-11 does not result in significantly increased DNA synthesis or Ig secretion by purified B cells alone or B cells cultured with Staphylococcus Cowan I, a T-cell-independent B-cell mitogen. In contrast, purified B cells cultured in the presence of pokeweed mitogen (PWM), irradiated T cells, and monocytes show increased DNA synthesis at day 3 and increased IgG and IgM secretion at day 7 of culture; addition of IL-11 further augments Ig secretion without change in DNA synthesis, an effect that can only be partially blocked by monoclonal antibody to IL-6. Similar experiments confirmed that increased IgG secretion was demonstrable when either IL-11 or IL-6 was added to B cells + CD4+/45RA- T cells + monocytes + PWM; in contrast, Ig secretion was low and equivalent when CD4+/45RA+ T cells were cultured with B cells+monocytes+PWM with or without IL-6 or IL-11. Neither IL-6 nor IL-11 could significantly increase phytohemagglutinin (PHA)-induced DNA synthesis by CD4+/45RA- or CD4+/45RA+ T cells. Although PWM or IL-11 induced IL-6 mRNA expression in both CD4+/45RA- T cells and monocytes, in neither cell did IL-11 increase IL-6 mRNA expression over that noted to PWM alone. These observations support the view that IL-11 promotes differentiation of human B lymphocytes only in the presence of accessory T cells and monocytes and that a minor component of this effect may be through stimulation of IL-6 production by CD4+/45RA- T cells and monocytes.