The alternative splicing of human Fc gamma RII mRNA is regulated by activation of B cells with mIgM cross-linking, interleukin-4, or phorbolester.
The human type two IgG binding receptors (Fc gamma RII) are encoded by three genes (Fc gamma RIIA, -B and C) resulting in at least six protein isoforms generated by alternative mRNA splicing. Surface expression of Fc gamma RII has been shown to be modulated during B cell activation, although data characterizing the isoform(s) expressed are not available. The extracellular as well as the transmembrane domains of various Fc gamma RII are highly homologous. Only the intracellular domains vary between the different Fc gamma RII isoforms, suggesting differences in signal transduction. Using reverse transcriptase and polymerase chain reaction of mRNA obtained from resting tonsil B cells, we show that the majority of Fc gamma RII mRNA species to be of b2 type, although b1 type and a low level of Fc gamma RIIa type are also present. Culturing the cells for 18 h in the presence of 2.5 U/ml interleukin-4 or 10 micrograms/ml affinity-purified anti-IgM F(ab')2 fragments induced a switch in alternative splicing, resulting in a significant increase of Fc gamma RIIb1 mRNA expression, while the synthesis of Fc gamma RIIb2 mRNA was down-regulated. Stimulation of B cells with 100 ng/ml phorbol 12-myristate 13-acetate induced similar alteration, although only after 48-h treatment. The accumulation of Fc gamma RIIb1 and the reduction of both Fc gamma RIIb2 and Fc gamma RIIa mRNA in activated cells is accompanied by the enhanced expression of Fc gamma RII on the cell surface, representing most probably the Fc gamma RIIb1 isoform. Heat-aggregated IgG inhibited the anti-IgM-induced proliferation of resting but not that of activated B cells, suggesting that aggregation of Fc gamma RIIb2 constitutively expressed on resting B cells might be responsible for the prevention of inadequate activation of resting B cells.
Laboratory of Immunoregulation, Vienna International Research Cooperation Center at SFI, Austria.
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G
Sármay
Z
Z
Rozsnyay
G
G
Koncz
A
A
Danilkovich
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J
Gergely
D017398:Alternative Splicing / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000502:physiology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000166:cytology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007075:Immunoglobulin M; D012333:RNA, Messenger; D017452:Receptors, IgG; D015847:Interleukin-4; D013755:Tetradecanoylphorbol Acetate