Trafficking of the Igα/Igβ Heterodimer with Membrane Ig and Bound Antigen to the Major Histocompatibility Complex Class II Peptide-loading Compartment

Bruce K Brown,Chang Li,Paul C Cheng,Wenxia Song

doi:10.1074/jbc.274.16.11439

Abstract

The binding of antigen to the B cell antigen receptor (BCR) initiates two major cellular events. First, upon cross-linking by antigen, the BCR induces signal transduction cascades leading to the transcription of a number of genes associated with B cell activation. Second, the BCR internalizes and delivers antigens to processing compartments, where processed antigenic peptides are loaded onto major histocompatibility complex (MHC) class II molecules for presentation to T helper cells. The BCR consists of membrane Ig (mIg) and Igalpha/Igbeta heterodimer (Igalpha/Igbeta). The Igalpha/Igbeta, the signal transducing component of the BCR, has been indicated to play a role in antigen processing. In order to understand the function of the Igalpha/Igbeta in antigen transport, we studied the intracellular trafficking pathway of the Igalpha/Igbeta. We show that in the absence of antigen binding, the Igalpha/Igbeta constitutively traffics with mIg from the plasma membrane, through the early endosomes, to the MHC class II peptide-loading compartment. Cross-linking the BCR does not alter the trafficking pathway; however, it accelerates the transport of the Igalpha/Igbeta to the MHC class II peptide-loading compartment. This suggests that the Igalpha/Igbeta heterodimer is involved in BCR-mediated antigen transport through the entire antigen transport pathway.

Highlights

B cells process and present antigens to T cells in order to initiate T cell-dependent antibody responses
B cells mIgM and bound antigens are internalized from the plasma membrane (PM) into the early endosomes and are subsequently delivered to the MIIC, where they meet newly synthesized class II molecules transported from the trans-Golgi network
Co-localization of the Ig␣/Ig␤ Heterodimer and Membrane Ig (mIg)-antigen Complexes in the MIIC—Using subcellular fractionation, we showed that the Ig␣/Ig␤ is internalized from the PM into the early endosomes and subsequently moves to the dense vesicles that include the MIIC

Summary

Introduction

B cells process and present antigens to T cells in order to initiate T cell-dependent antibody responses. We describe the intracellular transport pathway of the Ig␣/Ig␤ heterodimer in B cells and show that the Ig␣/Ig␤ constitutively traffics with mIg and bound antigen from the PM through the endocytic pathway to the MIIC, where functional peptide-class II complexes are formed. Intracellular Trafficking of the Ig␣/Ig␤ Heterodimer—Previously, using subcellular fractionation, we isolated and characterized the MIIC [9] and described the intracellular transport pathway of mIg and bound antigen in B cells [30].

Results

Conclusion