AP2 adaptor complex-dependent internalization of CD5: Differential regulation in T and B cells

Academic Article

Abstract

  • CD5 is a key regulator of Ag receptor-mediated activation, selection, and differentiation in both T and B cells. Accumulating evidence indicates that lymphocyte activation and selection are sensitive to variations in levels of CD5 on the cell surface. We now show that CD5 expression on the surface of B and T cells is regulated posttranslationally by direct interaction with the μ subunit of the AP2 adaptor complex that links transmembrane proteins to clathrin-coated pits. CD5 is rapidly internalized from the cell surface in lymphoid cell lines, mature splenic T and B cells, and peritoneal CD5 B cells following monovalent or bivalent ligation of the receptor. We mapped the μ subunit binding site on CD5 to Y and determined that the integrity of this site was necessary for CD5 internalization. Cross-linking of the Ag receptor with intact Abs inhibited CD5 internalization in B cells, but had the opposite effect in T cells. However, if F(ab′) Abs were used to stimulate the Ag receptor in B cells, the effect on CD5 internalization was now similar to that observed in T cells, indicating that signals through the Ag receptor and FcR regulate CD5 endocytosis in B cells. This was confirmed using an FcγRIIB1-deficient B cell line. The ability to differentially alter posttranslational CD5 expression in T and B cells is likely to be key in regulation of Ag receptor signaling and generation of tolerance in T and B lymphocytes. 2 2 2 + 429
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Lu X; Axtell RC; Collawn JF; Gibson A; Justement LB; Raman C
  • Start Page

  • 5612
  • End Page

  • 5620
  • Volume

  • 168
  • Issue

  • 11