Signaling Difference between Class IgM and IgD Antigen Receptors^a

Abstract

Most mature B lymphocytes coexpress two classes of antigen receptor, IgM and IgD. The differences in the signal transduction from the two receptors are still a matter of controversy. We have analyzed B-cell lines expressing IgM or IgD antigen receptors with the same antigen specificity. Cross-linking of these receptors with either antigen or class-specific antibodies results in the activation of protein tyrosine kinases and the phosphorylation of the same substrate proteins. The kinetic and intensity of phosphorylation, however, was quite different between the two receptors when they were cross-linked by antigen. In membrane IgM-expressing cells, the substrate phosphorylation reached a maximum after one minute and diminished after 60 minutes, whereas in the membrane IgD-expressing cells, the substrate phosphorylation increased further over time, reaching its maximum at 60 minutes and persisting longer than 240 minutes after exposure to antigen. Recently prolonged signaling has been found to be responsible for signaling differences between tyrosine kinase receptors using otherwise similar signaling routes. Thus, the duration of a signal may be an important biological feature of signal-transducing cascades.

Role of Phosphatidylinositol 3-Kinase in Anti-IgM- and Anti-IgD-Induced Apoptosis in B Cell Lymphomas

“…Although mechanisms of anti-signaling in B cell lines have been extensively studied, the role of the sIgD receptor is largely unknown (54). Furthermore, although the fundamental differences in these anti--vs anti-␦-stimulated outcomes have been known for some time, the intervening signals involved in eliciting the observed responses are unknown.…”

B cells from patients with systemic lupus erythematosus display abnormal antigen receptor-mediated early signal transduction events.

“…Both "precalcium" segments are qualitatively, but not quantitatively, identical, since their regulatory mechanisms might differ (49). The "postcalcium" events might be quite dissimilar as well (70, 71). ]…”

“…An equal number of PBMC enriched in B cells was stimulated with 20 g of the F(abЈ) 2 fragment of a goat anti-human Ab for 60 s, a time that has been known to be required for maximal anti-sIgM-induced PTK activity (49). After lysing the cells, an equal amount of protein was electrophoretically separated on gels, transferred on membranes and blotted with an anti-phosphotyrosine-HRPO-conjugated mAb.…”

B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk

“…These two receptors have distinct signaling functions and diffusion behaviors on the B cell surface but the molecular basis for these differences is poorly understood (Kim and Reth, 1995; Treanor et al, 2010). The cross-linking model (CLM) assumes that most of the 100,000 BCR complexes on the surface of a B cell are monomeric and that cross-linking of two BCR monomers by a polyvalent antigen initiates the signaling process (Metzger, 1992).…”