Distinct IL-4 response mechanisms of the MHC gene A alpha in different mouse B cell lines.
Interleukin-4 (IL-4) is a multipotent cytokine which stimulates proliferation of B and T lymphocytes, induces B lymphocyte expression of major histocompatibility complex (MHC) class II molecules and Fc epsilon R II (CD23) molecules, and promotes immunoglobulin class switching to IgE and IgG1. The mechanisms by which IL-4 induces these changes are unclear. To study the basis for heterogeneity in induction of class II MHC proteins observed in splenic B cells, three mouse B cell lines were treated with IL-4, and the response of MHC class II A alpha mRNA was analyzed. Each of the three cell lines responded with a distinctive profile. In one line, 70Z/3, A alpha mRNA was induced greater than 10 fold by 65 hr of IL-4 stimulation. Additional studies showed that A alpha mRNA was stabilized by IL-4 treatment of 70Z/3 cells, and that changes in gene transcription accounted for little of the increase in mRNA levels. A second line, WEHI.231, was shown to increase A alpha mRNA levels 4 fold after 48 hr of IL-4 treatment. In contrast to 70Z/3, when A alpha mRNA stability in the IL-4 treated WEHI.231 cells was compared to untreated cells, no difference was observed, IL-4 treatment induced A alpha transcription. The third cell line, M12.4.1, expressed high basal levels of A alpha, and these levels increased only slightly following IL-4 stimulation. The small increase correlated with a comparable transcriptional response. These data shown that the nature of the A alpha gene response to IL-4 differs among B cell lines. This heterogeneity of response is consistent with responses in total splenic B cells, and with the existence of functionally distinct subpopulations of B cells.
Whitley
M Z
MZ
Department of Cancer Biology, Harvard School of Public Health, Boston, MA.
Cheng
H L
HL
Tomasi
T B
TB
Boothby
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005802:Genes, MHC Class II; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000949:Histocompatibility Antigens Class II; D012333:RNA, Messenger; D015847:Interleukin-4