Interactions between lymphocyte membrane molecules. I. Interaction between B lymphocyte surface IgM and Fc IgG receptors requires ligand occupancy of both receptors.

Abstract

The independent B lymphocyte surface membrane receptors IgM and Fc IgG receptors were evaluated for interactions using immunoflourescence. Ligand [F(ab')2 anti-mu]-induced capping of surface IgM resulted in capping of Fc IgG receptors only if the latter were occupied during the capping process by: (a) soluble antigen-antibody complexes that themselves provided insufficient cross-linking to result in capping; or (b) monomeric IgG at physiologic concentrations (or less) either purified or as normal serum. Ligand-induced capping of Fc IgG receptors did not result in capping of surface IgM occupied by monomeric F(ab') anti-mu. Control experiments showed that ligand binding to or capping of only one of these two receptors has no effect on the other, and that there were no cross-reactions. The interaction appears specific in that ligand-induced capping of surface IgM did not induce capping of ligand-occupied surface IgD or I-A antigens. Thus, there appears to be a specific interaction between ligand-bound surface IgM and ligand-bound Fc IgG receptors on the B lymphocyte surface. The results also indicate that binding of monomeric IgG produces a reversible alteration in the Fc IgG receptor leading to association with ligand-bound surface IgM. Because Fc IgG receptors are continuously exposed to monomeric IgG in vivo, these results suggest that whenever surface IgM is involved in a B lymphocyte response to an immunologic stimulus, the Fc IgG receptor is also involved.

Structural Bases of Fcγ Receptor Functions

“…Although the functional significance of capping is unknown, it is conceivable that the ability of the B lymphocyte-specific FcyRIIbl to cap allows this receptor to play a role in the formation of an activation complex induced by antigen or antibodies to certain cell surface molecules, such as mlg or MHC class II. The fact that, in B lymphocytes, antibody-induced polar redistribution of these molecules induces co-capping of FcyR (Dickler & Sachs 1974, Dickler & Kubicek 1981 supports this hypothesis which is also compatible with the phosphorylation of FcyRIIbl observed in A20/2J lymphoma B cells activated by anti-Ig F(ab')2 (Hunziker et al 1990).…”

Natural Killer and T‐Cell Potentiation by Monoclonal IgG against Natural Killer Cell FcR(IgG) or the T3 Complex

“…Such an interaction increases the cross-linking ability of the antibodies and may cause a polymerization state of FcR that results in new binding forces between FcR and other cell-surface receptors [7]. The capacity of FcR to interact with cell-surface receptors has been investigated by Dickler [3,4,5], demonstrating that anti-la antibodies in the mouse modulate FcR activity and that this interaction does not depend on an intact Fc region. F(ab')T anti-IgD treatment gave [gD and FcR co-capping provided the latter were occupied by soluble immune complexes, in contrast to IgM co-capping, which required slightly different conditions |5].…”

“…The triggering function of FcR in several systems [14], the inductibility of such receptors [14], the Ig-like character of several other cell surface receptors [2,32], and the clear affinity between some receptors and FcR in the intact cell membrane [3,4,5] could be incorporated into a "pro-receptor" hypothesis for FcR as suggested by Ramasamy et al |19]. An initial cellcell interaction by recognition and adhesion type receptors may be followed by a second interaction that activates signal propagation by a Ca-* flux or hy mobilization of Ca-^^ from intracellular depots.…”

Signal Transduction Pathways Involved in B‐Cell Induction

“…It should also be mentioned that crosslinking of sIg leads to co-capping of additional molecules, some of which are well characterized, namely MHC class II (Dickler & Kubicek 1981), FcyRII (Amigorena et al 1992), and cytoplasmic plV' (Graziadei et al 1990). All these molecules may be important in signal transduction.…”