IgE-enhancing activity directly and selectively affects activated B cells: evidence for a human IgE differentiation factor.
T cells from highly atopic individuals spontaneously secrete in vitro a factor that specifically induces IgE synthesis from normal human B cells. We investigated the effects of such T cell supernatants derived from atopic individuals (TCSN-A) on functionally distinct B cell subsets to determine at what developmental stage B cells become responsive to this IgE-enhancing activity. B cells from normal and allergic donors were separated into subsets of small resting and large activated cells by density centrifugation or unit gravity sedimentation. When stimulated by TCSN-A, large activated B cells made more IgE than small resting B cells. The difference was as much as 3300% in comparing these subsets from allergic donors. Similarly, resting B cells stimulated by Staphylococcus aureus Cowan I (SAC) made 52 to 125% more IgE in response to TCSN-A than unstimulated small resting B cells. However, IgE production from large B cells, already activated in vivo, was not enhanced by the addition of SAC. Notably, the IgE level synthesized by in vivo large activated B cells from allergic persons was markedly greater than that seen with similar cells from normal donors, whereas resting B cells purified from allergic and normal donors produced comparable levels of IgE in response to TCSN-A. These results suggest that this enhancing activity functions as an IgE differentiation factor for activated B cells. This was further confirmed by the effects of TCSN-A on the IgM- and IgE-secreting EBV-transformed human B cell line K1D5. TCSN-A specifically enhanced IgE synthesis from these cells; TCSN from normal donors, IL 2, IFN-gamma, and BCGF did not. These results confirm that this activity functions as an IgE-specific differentiation factor, directly influencing activated B cells to synthesize IgE.
D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D008222:Lymphokines; D011947:Receptors, Antigen, B-Cell; D007073:Immunoglobulin E