A TYROSINE-BASED SIGNAL PRESENT IN IG-ALPHA MEDIATES B-CELL RECEPTOR CONSTITUTIVE INTERNALIZATION

B lymphocytes express Ag receptors (BCR) that are composed of ligand b inding subunits, the membrane Igs, associated with Ig alpha/Ig beta he terodimers. One main BCR function is to bind and to internalize Ags, P eptides generated from these internalized Ags may be presented to T ly mphocytes, Here, we have analyzed the involvement of BCR Ig alpha/Ig b eta components in BCR constitutive endocytosis. The role of Ig alpha s ubunit in BCR constitutive endocytosis was first determined in the con text of an IgM-based BCR, In contrast with BCR that contain wild-type Ig alpha, surface BCR lacking Ig alpha cytoplasmic domain were not con stitutively internalized. The respective roles of Ig alpha and Ig beta subunits were then analyzed by expressing chimeric molecules containi ng the cytoplasmic domains of either subunits in a B cell line. Only t he Ig alpha cytoplasmic domain contained an internalization signal tha t allowed constitutive endocytosis of Ig alpha chimeras via coated pit s and accumulation in sorting-recycling endosomes, This internalizatio n signal is contained in its immunoreceptor tyrosine-based activation motif, These results indicate that Ig alpha, through its immunorecepto r tyrosine-based activation motif, may account for the ability of IgM/ IgD BCR to constitutively internalize monovalent Ags.