Inhibitory mechanism of the proliferative responses of resting B cells: feedback regulation by a lymphokine (suppressive B-cell factor) produced by Fc receptor-stimulated B cells.
We investigated the effect of a lymphokine termed 'suppressive B-cell factor' (SBF), which is produced by FcR gamma (Fc receptor for IgG)-stimulated B cells or hybridoma TS4.44, and is known to suppress B-cell responses in vivo and in vitro by inhibiting their proliferation. Small B cells, fractionated by Percoll density gradient, from athymic nude mice (BALB/c) secreted SBF after binding EA (sheep erythrocytes sensitized with IgG mouse anti-sheep erythrocyte antibody), and the proliferation of small but not large B cells was preferentially suppressed by SBF in response to LPS in vitro. Proliferation of purified B cells from BALB/c nu/nu mice, induced by a synergistic interaction between F(ab')2 fragment of goat anti-mouse IgM antibody and B-cell stimulating factor (BSF1), was almost completely abrogated by the co-existence of SBF during the 72-hr culture period. However, the co-culture with SBF for the last 24 or 48 hr, as well as of B cells pretreated with SBF for 1 hr at 37 degrees, partially inhibited the growth response. These findings suggest that SBF operates on resting B cells and holds them in a resting state. This notion would be further supported by the fact that SBF inhibited G0-G1 transition. Taken together, we conclude that SBF acts on the early step of B-cell activation, thereby inhibiting B-cell growth. Arrest of resting B cells in the G0 phase and failure of an increase in functional receptors for BSF1 seem to be responsible for the suppression of B-cell responses.
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002453:Cell Cycle; D002455:Cell Division; D005260:Female; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG
D008222:Lymphokines; D011961:Receptors, Fc; D017452:Receptors, IgG