The role of Ig-α/β in B cell antigen receptor internalization

The B cell antigen receptor (BCR) is expressed on the surface of B lymphocytes where it can bind antigen then transmit signals which regulate activation growth and differentiation These signals can induce a number of cytoskeletal rearrangements leading to dynamic cellular processes including internalization of the bound antigen which is then processed and presented to T cells on MHC H The relative importance of regions within the Ig alpha and Ig beta cytoplasmic domains has been well studied in terms of signaling but their roles in BCR internalization and trafficking are less clear We hypothesize that the Ig alpha and Ig beta cytoplasmic domains is important for normal internalization and trafficking of the 4 chain BCR An Ig alpha and Ig beta deficient murine lymphoid cell line was used to express mIgM along with a panel of Ig alpha and Ig beta mutants in order to compare their internalization and subcellular localization Here we show that the Ig alpha and Ig beta cytoplasmic domains are each sufficient for internalization though Iga is dominant in this process We also show that the internalization signal is contained in a region past the first cytoplasmic tyrosine residue of Ig alpha and Ig beta Y176 and Y195 respectively We also show that a 4 amino acid motif normally contained within the Ig alpha ITAM is sufficient to rescue aberrant internalization In terms of receptor trafficking each cytoplasmic domain is sufficient for trafficking to lysosomal compartments but that a normal rate of trafficking likely requires the tandem effects of both Ig alpha and Ig beta (C) 2010 Elsevier B V All rights reserved