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 II. The relative importance of regions within the Igα and Igβ 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 Igα and Igβ cytoplasmic domains is important for normal internalization and trafficking of the 4 chain BCR. An Igα and Igβ deficient murine lymphoid cell line was used to express mIgM along with a panel of Igα and Igβ mutants in order to compare their internalization and subcellular localization. Here we show that the Igα and Igβ cytoplasmic domains are each sufficient for internalization, though Igα is dominant in this process. We also show that the internalization signal is contained in a region past the first cytoplasmic tyrosine residue of Igα and Igβ, Y176 and Y195 respectively. We also show that a 4 amino acid motif normally contained within the Igα 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 Igα and Igβ.
Jang
Caren
C
Department of Zoology, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
Machtaler
Steven
S
Matsuuchi
Linda
L
D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D051925:CD79 Antigens / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D009154:Mutation; D021381:Protein Transport; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D051925:CD79 Antigens; D011947:Receptors, Antigen, B-Cell