Expression of Interleukin-4 Receptors on Early Human B-Lineage Cells

Abstract

Interleukin-4 (IL-4) regulates multiple stages of the antigen-dependent phase of B-cell development. However, its precise role in regulating B lymphopoiesis in bone marrow is not as well defined. We examined whether surface IgM- normal and leukemic human B-cell precursors (BCP) expressed IL-4 receptors using biotinylated IL-4. Constitutive expression of IL-4 receptors was detected on both normal and leukemic BCP. A higher percentage of normal BCP (82% +/- 15%) expressed IL-4 receptors compared with leukemic BCP (44% +/- 8%). Using mean fluorescent intensity as an indicator of receptor level on the IL-4 receptor positive cells, normal (91 +/- 41) and leukemic (44 +/- 37) BCP expressed comparable numbers of receptors. IL-4 induced the expression of CD23 on 30% of the leukemic BCP cases examined. IL-4 induced CD23 on surface IgM+ fetal bone marrow lymphoid cells but not on the surface IgM- normal BCP, despite the presence of detectable receptors on the surface IgM- cells. IL-4 did not stimulate proliferation of normal BCP, nor could it enhance the effect of recombinant IL-7 or low molecular weight B-cell growth factor. However, IL-4 increased the expression of surface IgM and surface Ig kappa on in vitro differentiated pre-B cells. Our collective results identify no role for IL-4 in the proliferation of normal or leukemic BCP, but identify a role in the enhancement of surface Ig expression during pre-B to B-cell differentiation.