CO-CROSS-LINKING FC-EPSILON-RII/CD23 AND B-CELL SURFACE-IMMUNOGLOBULIN MODULATES B-CELL ACTIVATION

Previous studies have shown that a highly multivalent from of anti-IgD or anti-IgM, prepared by conjugating the respective antibodies to dextran, causes extensive B cell proliferation with ng/ml concentrations of the anti-immunoglobulin (Ig). A modification of this system has been exploited to investigate the effect of co-crosslinking the Fc-epsilon-RII and surface Ig by binding DNP to the dextran backbone (DNP-dextran) and employing a DNP-specific monoclonal IgE of either rat or mouse origin. Addition of anti-IgD-(H-delta(a)/1)[DNP-dextran] or anti-IgM-[DNP-dextran] to purified. resting murine B ells resulted in B cell proliferation over a broad dose (0.03-30-mu-g/ml). Addition of DNP-specific rat or mouse IgE dramatically modulated the proliferative response. Proliferation in response to doses greater than 0.3-mu-g/ml H-delta(a)/1-[DNP-dextran] was consistently reduced in a dose-dependent manner in the presence of increasing amounts of IgE while proliferation to lower concentrations of H-delta(a)/1-[DNP-dextran] was slightly enhanced or not influenced at all by the IgE anti-DNP Interleukin-4 (IL-4) significantly increased the IgE effect, in line with its known enhancing effects on Fc-epsilon-RII levels. Experiments measuring Ig production rather than proliferation demonstrated that in the presence of IgE anti-DNP, B cells produced lower amounts of immunoglobulin (IgG1 or IgM) in response to an anti-Ig signal. Control experiments demonstrated that the IgE effect on proliferation was blocked by monoclonal anti-Fc-epsilon-RII, but not anti-Fc-gamma-RII, thus demonstrating the necessity for IgE/Fc-epsilon-RII interaction. In addition, the necessity for co-crosslinking was shown by the inability of IgE anti-DNP to affect the proliferative response to H-delta(a)/1-dextran even in the presence of various doses of DNP-dextran. These results demonstrate that co-crosslinking of sIg and the Fc-epsilon-RII results in an altered B cell response to anti-Ig mediated activation. IL-4 does not ablate this inhibition, in contrast to the effect of co-crosslinking Fc-gamma-RII and surface Ig, suggesting a model whereby IgE can modulate its own production.