Interleukin 4 receptors on normal human B lymphocytes: characterization and regulation.
Human interleukin 4 (IL 4) up-regulates the expression of CD23 on both resting and "in vivo" activated B cells but induces proliferation and/or differentiation only on "in vitro" activated B lymphocytes. Resting B cells express 360 high-affinity IL 4 receptors (R) per cell (Kd = 25-75 pM). Activation of resting B cells with anti-IgM antibody or Staphylococcus aureus Cowan I (SAC) results in a two-to-threefold increase of IL 4R number without alteration of IL 4R affinity for IL 4. Flow cytometric analysis of biotinylated IL 4 binding shows that IL 4R expression is up-regulated on virtually all anti-IgM-stimulated B cells, but only on a subpopulation of larger cells among SAC-activated B lymphocytes. Culturing cells for 40 h with optimal concentrations of IL 4 does not significantly affect IL 4R levels on resting and anti-IgM-preactivated B lymphocytes but triples IL 4R levels on SAC-preactivated B cells. Removal of IL 4 from cell cultures results in a two-to-fourfold increase of IL 4R levels 2 h later, suggesting an increase in IL 4R turnover. Resting and activated B cells degrade 125I-labeled IL 4 at 37 degrees C. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of IL 4 binding molecules on resting, "in vivo" activated and anti-IgM-activated B cells reveals the same three species of 130, 80-75, 70-65 kDa. Thus, IL 4 displays its different biological activities on resting and activated B cells through IL 4R of the same affinity, gross biochemical structure and ability to mediate IL 4 degradation.
Zuber
C E
CE
UNICET, Laboratory for Immunological Research, Dardilly, France.
Galizzi
J P
JP
Vallé
A
A
Harada
N
N
Howard
M
M
Banchereau
J
J
D001402:B-Lymphocytes / Q000502:physiology*; D003432:Cross-Linking Reagents; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000502:physiology*; D008213:Lymphocyte Activation; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000502:physiology*; D015854:Up-Regulation
D003432:Cross-Linking Reagents; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4