THE RESPONSE OF HUMAN B-CELLS TO INTERLEUKIN-4 IS DETERMINED BY THEIR STAGE OF ACTIVATION AND DIFFERENTIATION

The effect of purified‐ recombinant human interleukin 4 (IL‐4) on proliferation and IgM secretion of normal and malignant human B cells was studied. IL‐4 was found to co‐stimulate the proliferation of splenic B cells in the presence of anti‐Ig coupled to polyacrylamide beads (anti‐Ig beads) for a period of 4 days In contrast. IL‐4 had little co‐stimulatory effect on the proliferative response of splenic B cells to the more potent mitogen Staphylococcus aureus Cowan strain I (SAC) Moreover, IL‐4 inhibited interleukin: 2(IL‐2) induced proliferation of cells co‐stimulated with SAC Mitogen‐induced pre‐activation of B cells in the presence of IL‐4 resulted in a reduction in subsequent IL‐2‐induced IgM secretion without significantly affecting proliferation Human B‐cell tumours were also cultured over a 2‐3 day period in the presence of anti‐Ig beads plus IL‐2. or IL‐4orboth IL‐2 and IL‐4. IL‐4 inhibited IL‐2‐induced proliferation in all cases of B‐cell chronic lymphocytic leukaemia (B‐CLL)and the majority of cases of low‐grade lymphoma (LGL)and hairy cell leukaemia (HCL). These findings suggest that IL‐4 has stimulatory actions on resting B cells, most evident in the presence of submaximal co‐mitogenic signals, and inhibitory actions on actuated B cells, especially antagonism of the effects of IL‐2. Copyright © 1990, Wiley Blackwell. All rights reserved