Effects of various forms of monoclonal anti-Fc gamma R II (2.4G2) on B lymphocyte responses.
The effects of monoclonal anti-Fc gamma R II (2.4G2) in various forms on B lymphocyte proliferation and antibody (mu) secretion in vitro were evaluated. Soluble native 2.4G2 did not stimulate or inhibit the responses of B lymphocytes, either unstimulated or stimulated with rabbit F(ab')2 anti-mouse mu (anti-mu) plus lymphokines (the supernatant of Concanavalin A stimulated rat spleen cells). The failure of native 2.4G2 to affect responses was observed over a broad range of concentrations, and even when the B lymphocytes were incubated with the 2.4G2 for 24 hr prior to stimulation with anti-mu and lymphokines. Similarly, soluble chemically cross-linked 2.4G2 failed to affect B lymphocyte responses. Binding studies indicated that this failure was not due to a lack of binding and suggested that the polymerized 2.4G2 was cross-linking at least four Fc gamma R II. Larger multimers of 2.4G2 could not be evaluated due to a loss of binding activity. In contrast to the above results, 2.4G2 which was capable of extensively cross-linking Fc gamma R II (2.4G2 bound to Sepharose) or of cross-linking Fc gamma R II to surface IgM (2.4G2 hetero-cross-linked with anti-mu) specifically inhibited B lymphocyte responses to anti-mu and lymphokines. Antibody secretion was affected more than proliferation. These results provide additional evidence that Fc gamma R II regulate the responses of B lymphocytes, and suggest that cross-linking of more than four Fc gamma R II is necessary to generate the inhibitory signal. Further, the results indicate that the ligand does not have to be internalized in order to generate the regulatory signal. Finally, the results with the heterodimer suggest that it may be possible to regulate a particular antibody response using anti-Fc gamma R II cross-linked to antigen or to anti-receptor antibody (e.g. an anti-idiotype).
Dickler
H B
HB
Immunology Branch, National Institutes of Health, Bethesda, MD 20892.
Kubicek
M T
MT
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000943:Antigens, Differentiation / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002455:Cell Division; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D011961:Receptors, Fc / Q000276:immunology*; D017452:Receptors, IgG; D012685:Sepharose / Q000276:immunology
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D007148:Immunoglobulin mu-Chains; D011961:Receptors, Fc; D017452:Receptors, IgG; D012685:Sepharose