Expression of IL-9 receptor alpha chain on human germinal center B cells modulates IgE secretion.

Abstract

IL-9 has been shown to affect the differentiation pathway of different cell types. However, its potential role in the maturation pathway of antigen-driven B-cell differentiation and its functional effects remain unknown. To characterize IL-9 receptor alpha chain (IL-9R alpha) expression on human tonsillar B cells at different maturational stages, and to assess its effect on IgE production. Freshly purified human tonsillar B cells were fractionated into 3 populations: low-density (LD), medium-density, and high-density cells. Expression levels of IL-9R alpha were determined by using immunohistochemistry and flow cytometry. IL-9R alpha(high)-expressing cells were stimulated with IL-9 in the presence or absence of IL-4, and IgE release was measured by ELISA. IL-9R alpha was expressed on human LD tonsillar B cells, with an ability to transduce signals through activation of signal transducer and activator of transcription 3 and 5. Although IL-9 was unable to induce IgE secretion by itself, it potentiated IL-4-mediated IgE production from LD cells. Moreover, increased IgE was paralleled by an upregulation of IL-9R alpha and CD27, with the latter a memory B-cell marker implicated in increased IgE secretion. These results highlight a crucial role for IL-9 in modulating T-cell-dependent B-cell differentiation and establish a new paradigm for understanding the synergistic role of T(H)2 cytokines and their modulatory effect on B-cell maturation and IgE production. IL-9 appears to be involved in memory B-cell differentiation and T(H)2-mediated allergic diseases such as asthma.