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.
Goroff
D K
DK
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Finkelman
F D
FD
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007072:Immunoglobulin D / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D017455:Receptors, IgE; D017452:Receptors, IgG
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D007072:Immunoglobulin D; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D017455:Receptors, IgE; D017452:Receptors, IgG