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 1 (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-4 or both 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 activated B cells, especially antagonism of the effects of IL-2.
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
D W
DW
Maher
B L
BL
Pike
A W
AW
Boyd
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD / Q000502:physiology; D000943:Antigens, Differentiation / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018956:CD5 Antigens; D002454:Cell Differentiation; D002455:Cell Division; D015536:Down-Regulation; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology*; D007700:Kinetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology; D008213:Lymphocyte Activation; D008223:Lymphoma / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018956:CD5 Antigens; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D015847:Interleukin-4