Cooperative interaction of Igα and Igβ 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 Igα/Igβ heterodimer, facilitates antigen processing by accelerating antigen targeting to the processing compartment. Previous reports showed that Igα or Igβ alone is competent for internalizing antigens. However, both Igα and Igβ 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 Igα or Igβ, we studied the roles of the cytoplasmic tails of Igα and Igβ in BCR‐mediated antigen transport. The Igβ chimera rapidly moves through the endocytic pathway to lysosomes, while the Igα chimera slows down this movement. The Igα, but not the Igβ chimera, is required for an increase in the turnover rate of the chimeras in response to stimulation. Only when Igα and Igβ chimeras are co‐expressed do the chimeras rapidly and specifically target antigens to the processing compartment. These findings suggest that Igα and Igβ play distinct roles in BCR trafficking, and the cooperative interaction of Igα and Igβ controls and regulates the kinetics and specificity of antigen targeting.