Activation of B cells in vivo by a Fab/Fc fragment of a monoclonal anti-IgD antibody requires an interaction between the antibody fragment and a cellular IgG Fc receptor.

To investigate activation of B lymphocytes in vivo by an interaction between B cell surface Ig (sIg) and an anti-Ig antibody, we compared the abilities of a divalent IgG2b anti-IgD mAb, H delta a/1, and its univalent Fab/Fc fragment to enhance B cell sIa expression in vivo. The Fab/Fc fragment consists of a single Fab linked to Fc, and can interact with C and cellular Fc receptors. Although injection of BALB/c mice with either intact H delta a/1 or H delta a/1 Fab/Fc enhanced splenic B cell sIa expression, Ia expression was enhanced more by intact H delta a/1. Furthermore, injection of mice with 24G2, a mAb to the B cell and macrophage IgG2b Fc receptor, completely blocked the ability of 20 to 500 micrograms of H delta a/1 Fab/Fc to enhance B cell sIa expression, but had no effect on enhancement of B cell sIa expression by 100 micrograms of intact H delta a/1. This effect of 24G2 was mediated by its blocking of IgG2b receptor function rather than simply by its binding to B lymphocytes, since a mAb to the B cell IgE receptor did not interfere with the ability of H delta a/1 Fab/Fc to enhance B cell sIa expression. The different effects of 24G2 on B cell activation by intact H delta a/1 and H delta a/1 Fab/Fc were not a result of differences in the abilities of the intact antibody and its Fab/Fc fragment to activate B cells, since 24G2 did not interfere with the ability of AMS-15, a IgG2a anti-IgD mAb, to slightly increase B cell sIa expression. These observations indicate that a univalent ligand for B cell sIg can activate B lymphocytes in vivo through an IgGFc-IgGFc receptor-dependent interaction.