Cooperativity and segregation of function within the Ig-α/β heterodimer of the B cell antigen receptor complex

Abstract

The B cell antigen receptor complex contains heterodimers of Ig-α and Ig- β. The cytoplasmic tails of each of these chains contain two conserved tyrosines, phosphorylation of which initiates the signal transduction cascades activated by the receptor complex. Although the cytoplasmic domains of Ig-α and Ig-β have been expressed individually and demonstrated to be competent signal transduction units, we postulated that within the context of a heterodimer, Ig-α and Ig-β could have new, complementary or even synergistic functions. Therefore we developed a system to compare the signal transducing capacities of dimers of Ig-α/Ig-α, Ig-β/Ig-β, or Ig-α/Ig- β. This was done by fusing the extracellular and transmembrane domains of either human platelet-derived growth factor receptor (PDGFR) α or β to the cytoplasmic tail of either Ig-α or Ig-β. Three cell lines expressing PDGFRβ/Ig-α, PDGFRβ/Ig-β, or PDGFRα/Ig-β together with PDGFRβ/Ig-α were established in the murine B cell line A20 IIA1.6. While aggregation of each dimer by itself could induce the tyrosine phosphorylation of cellular substrates, only aggregation of the heterodimer induced the phosphorylation of substrates similar in range and intensity to that induced by the endogenous B cell antigen receptor complex. Interestingly, Ig-β remarkably enhanced the rapidity (T(max) decreased from 5 to 1 min) and intensity (greater than 10-fold enhancement) of Ig-α phosphorylation. Conversely, the phosphorylation of Ig-β was reduced to undetectable levels when co- aggregated with Ig-α. The enhancement of Ig-α phosphorylation by Ig-β correlated with a lowering of the stimulation threshold for tyrosine kinase activation.