COOPERATIVITY AND SEGREGATION OF FUNCTION WITHIN THE IG-ALPHA BETA HETERODIMER OF THE B-CELL ANTIGEN RECEPTOR COMPLEX/

The B cell antigen receptor complex contains heterodimers of Ig-alpha and Ig-beta. The cytoplasmic tails of each of these chains contain two conserved tyrosines, phosphorylation of which initiates the signal tr ansduction cascades activated by the receptor complex. Although the cy toplasmic domains of Ig-alpha and Ig-beta have been expressed individu ally and demonstrated to be competent signal transduction units, we po stulated that within the context of a heterodimer, Ig-alpha and Ig-bet a could have new, complementary or even synergistic functions. Therefo re we developed a system to compare the signal transducing capacities of dimers of Ig-alpha/Ig-alpha, Ig-beta/Ig-beta, or Ig-alpha/Ig-beta. This was done by fusing the extracellular and transmembrane domains of either human platelet-derived growth factor receptor (PDGFR) alpha or beta to the cytoplasmic tail of either Ig-alpha or Ig-beta. Three cel l lines expressing PDGFR beta/Ig-alpha, PDGFR beta/Ig-beta, or PDGFR a lpha/Ig-beta together with PDGFR beta/Ig-alpha were established in the murine B cell line A20 IIA1.6. While aggregation of each dimer by its elf could induce the tyrosine phosphorylation of cellular substrates, only aggregation of the heterodimer induced the phosphorylation of sub strates similar in range and intensity to that induced by the endogeno us B cell antigen receptor complex. Interestingly, Ig-beta remarkably enhanced the rapidity (T-max decreased from 5 to 1 min) and intensity (greater than 10-fold enhancement) of Ig-alpha phosphorylation. Conver sely, the phosphorylation of Ig-beta was reduced to undetectable level s when co-aggregated with Ig-alpha. The enhancement of Ig-alpha phosph orylation by Ig-beta correlated with a lowering of the stimulation thr eshold for tyrosine kinase activation.