REGULATION OF ITAM SIGNALING BY SPECIFIC SEQUENCES IN IG-BETA B-CELL ANTIGEN RECEPTOR SUBUNIT

B cell antigen receptors (BCR) are composed of an antigen binding subu nit, the membrane Ig, and Ig-alpha/Ig-beta heterodimers, that contain a transducing motif named ITAM for ''immuno-receptor tyrosine-based ac tivation motif.'' Ig-alpha and Ig-beta ITAMs only differ by four amino acids located before the second conserved tyrosine (DCSM in Ig-alpha and QTAT in Ig-beta), which determine the in vitro association of Ig-a lpha with the src kinase fyn. We have previously shown that Ig-alpha a nd Ig-beta BCR subunits activate different signaling pathways by expre ssing, in B cells, Fc gamma RII chimeras containing the cytoplasmic ta ils of Ig-alpha or Ig-beta. We report here that the signaling capacity of Ig-beta ITAM is regulated by peptide sequences located inside (QTA T region) or outside the ITAM (flanking sequences), Furthermore, when isolated, Ig-alpha and Ig-beta ITAM have similar abilities as the enti re Ig-alpha tail and the whole BCR in triggering tyrosine kinase activ ation, an increase of intracellular calcium concentration as well as l ate events of cell activation as assessed by cytokine secretion, These data show that alterations that modify the ability of Ig-alpha and Ig -beta to interact in vitro with the src kinase fyn (switch between QTA T and DCSM) also determine signal transduction capabilities of these m olecules expressed in B cells.