Co‐crosslinking FcϵRII/CD23 and B cell surface immunoglobulin modulates B cell activation

Abstract

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 FcϵRII 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‐(Hδa/1)[DNP‐dextran] or anti‐IgM‐[DNP‐dextran] to purified, resting murine B cells resulted in B cell proliferation over a broad dose (0.03‐30 μg/ml). Addition of DNP‐specific rat or mouse IgE dramatically modulated the proliferative response. Proliferation in response to doses greater than 0.3 μg/ml Hδ^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 Hδ^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 FcϵRII 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‐FcϵRII, but not anti‐FcγRII, thus demonstrating the necessity for IgE/FcϵRII interaction. In addition, the necessity for co‐crosslinking was shown by the inability of IgE anti‐DNP to affect the proliferative response to Hδ^a/1‐dextran even in the presence of various doses of DNP‐dextran. These results demonstrate that co‐crosslinking of sIg and the FcϵRII 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 FcγRII and surface Ig, suggesting a model whereby IgE can modulate its own production.