The alternative splicing of human FcγRII mRNA is regulated by activation of B cells with mIgM cross‐linking, interleukin‐4, or phorbolester

The human type two IgG binding receptors (FcγRII) are encoded by three genes (FcγRIIA, ‐B and C) resulting in at least six protein isoforms generated by alternative mRNA splicing. Surface expression of FcγRII 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 Fcγ;RII are highly homologous. Only the intracellular domains vary between the different FcγRII 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 FcγRII mRNA species to be of b2 type, although b1 type and a low level of FcγRIIa type are also present. Culturing the cells for 18 h in the presence of 2.5 U/ml interleukin‐4 or 10 μg/ml affinity‐purified anti‐IgM F(ab')2 fragments induced a switch in alternative splicing, resulting in a significant increase of FcγRIIb1 mRNA expression, while the synthesis of FcγRIIb2 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 FcγRIIb1 and the reduction of both FcγRIIb2 and FcγRIIa mRNA in activated cells is accompanied by the enhanced expession of FcγRII on the cell surface, representing most probably the FcγRIIb1 isoform. Heat‐aggregated IgG inhibited the anti‐IgM‐induced proliferation of resting but not that of activated B cells, suggesting that aggregation of FcγRIIb2 constitutively expressed on resting B cells might be responsible for the prevention of inadequate activation of resting B cells.