Mechanisms of the interleukin 5-induced differentiation of B cells.
Interleukin 5 (IL5), a lymphokine produced by T cells, induces differentiation of B cell chronic leukemia BCL1-B20 cells into IgM-producing cells accompanied with growth arrest. To elucidate the intracellular mechanisms, the roles of Ca2+ mobilization and protein phosphorylation in the activation of the cells were examined. F(ab')2 fragment of anti-immunoglobulin (anti-Ig), which cross-links membrane-bound Ig, and calcium ionophore A23187 caused a rapid increase in the intracellular free calcium concentration [( Ca2+]i), whereas these stimulants did not give rise to differentiation of the cells. In contrast, treatment with IL5 did not affect either [Ca2+]i or the rates of Ca2+ uptake from the outside and release from the inside of the cells. Analysis by two-dimensional gel electrophoresis revealed that the in vitro phosphorylation of acidic 80-, 60-, and 45-kDa proteins was induced upon stimulation with IL5. Treatment with IL5 also caused a marked decrease in the in vitro phosphorylation of an acidic 100-kDa protein which was highly phosphorylated in the unstimulated state. Addition of phorbol 12-myristate 13-acetate (PMA) to the culture inhibited IL5-mediated differentiative responses. Therefore, these results suggest that Ca2+ mobilization is not involved but activities of stimulatory and inhibitory kinases may be involved in the IL5-mediated differentiation process.
Yamaguchi
N
N
Department of Biology, Kumamoto University Medical School.
Takahashi
T
T
Harada
N
N
Takatsu
K
K
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D007075:Immunoglobulin M / Q000096:biosynthesis; D015848:Interleukin-5 / Q000494:pharmacology*; D051379:Mice; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D007075:Immunoglobulin M; D015848:Interleukin-5; D011506:Proteins; D011494:Protein Kinases; D002118:Calcium