Cooperative interaction of Ig(alpha) and Ig(beta) of the BCR regulates the kinetics and specificity of antigen targeting.
Following the binding of antigens, the BCR transduces signals and internalizes antigens for processing and presentation, both of which are required for initiating an effective antibody response. The BCR, consisting of membrane Ig and Ig(alpha)/Ig(beta) heterodimer, facilitates antigen processing by accelerating antigen targeting to the processing compartment. Previous reports showed that Ig(alpha) or Ig(beta) alone is competent for internalizing antigens. However, both Ig(alpha) and Ig(beta) are required for BCR-enhanced antigen presentation. Using chimeric proteins containing the extracellular and transmembrane domains of human platelet-derived growth factor receptor fused with the cytoplasmic domain of Ig(alpha) or Ig(beta), we studied the roles of the cytoplasmic tails of Ig(alpha) and Ig(beta) in BCR-mediated antigen transport. The Ig(beta) chimera rapidly moves through the endocytic pathway to lysosomes, while the Ig(alpha) chimera slows down this movement. The Ig(alpha), but not the Ig(beta) chimera, is required for an increase in the turnover rate of the chimeras in response to stimulation. Only when Ig(alpha) and Ig(beta) chimeras are co-expressed do the chimeras rapidly and specifically target antigens to the processing compartment. These findings suggest that Ig(alpha) and Ig(beta) play distinct roles in BCR trafficking, and the cooperative interaction of Ig(alpha) and Ig(beta) controls and regulates the kinetics and specificity of antigen targeting.
D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D000077214:Becaplermin; D004705:Endocytosis; D007700:Kinetics; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D000077214:Becaplermin