Deregulated expression of c-fos disturbs proliferative responses of B cells to sIg cross-linking.
B cell activation by surface immunoglobulin (sIg) cross-linking is accompanied by transient expression of the c-fos protooncogene. This expression is strictly controlled in the B cells. To investigate a biological implication of the c-fos expression in the process of B cell activation by sIg cross-linking, we examined the proliferation of splenic B cells from H2-c-fos transgenic mice. Constitutive expression of the c-fos gene perturbs de novo synthesis of RNA and DNA in the B cells stimulated with anti-IgM antibody. Early events of signal transduction such as an increase in intracellular free calcium level and an induction of the endogenous immediate early genes (c-fos and c-myc) were apparently intact in those B cells. When the sIg stimulation of B cells was mimicked by the costimulation with 12-O-tetradecanoylphorbol 13-acetate and ionomycin, H2-c-fos B cells required higher concentrations of ionomycin for the optimal proliferative responses, suggesting that calcium-dependent signal transduction pathways are disturbed in those B cells. These results demonstrate a novel regulatory effect of c-fos protein on the proliferation of B cells mediated by sIg cross-linking.
Koizumi
T
T
Department of Immunology, ICMR, Kobe University School of Medicine, Japan.
Ochi
Y
Y
Kobayashi
S
S
Nakanishi
M
M
Tokuhisa
T
T
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D003432:Cross-Linking Reagents; D004247:DNA / Q000096:biosynthesis; D005786:Gene Expression Regulation; D016762:Genes, fos; D006183:H-2 Antigens / Q000235:genetics; D017874:Immediate-Early Proteins / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics; D012313:RNA / Q000096:biosynthesis; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology
D000888:Antibodies, Anti-Idiotypic; D003432:Cross-Linking Reagents; D006183:H-2 Antigens; D017874:Immediate-Early Proteins; D016760:Proto-Oncogene Proteins c-fos; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; C044203:anti-IgM; D015847:Interleukin-4; D015759:Ionomycin; D012313:RNA; D004247:DNA; D002118:Calcium