Acceleration of intracellular targeting of antigen by the B-cell antigen receptor: importance depends on the nature of the antigen-antibody interaction (original) (raw)
Related papers
The Journal of Immunology
Exogenous Ags taken up from the fluid phase can be presented by both newly synthesized and recycling MHC class II molecules. However, the presentation of Ags internalized through the B cell receptor (BCR) has not been characterized with respect to whether the class II molecules with which they become associated are newly synthesized or recycling. We show that the presentation of Ag taken up by the BCR requires protein synthesis in splenic B cells and in B lymphoma cells. Using B cells transfected with full-length I-Ak molecules or molecules truncated in cytoplasmic domains of their α- or β-chains, we further show that when an Ag is internalized by the BCR, the cytoplasmic tails of class II molecules differentially control the presentation of antigenic peptides to specific T cells depending upon the importance of proteolytic processing in the production of that peptide. Integrity of the cytoplasmic tail of the I-Ak β-chain is required for the presentation of the hen egg lysozyme dete...
Intracellular Targeting of Antigens Internalized by Membrane Immunoglobulin in B Lymphocytes
An important function of membrane immunoglobulin (mlg), the B cell antigen receptor, is to endocytose limiting quantities of antigen for efficient presentation to class II-restricted T cells. We have used a panel of mlg mutants to analyze the mechanisms of mlg-mediated antigen presentation, and specifically to explore the ability of mlg to target internalized antigen to intracellular processing compartments. Transfected mlgs carrying substitutions for the transmembrane Tyrs87 residue fail to efficiently present specifically bound antigen. However, these mutants internalize antigen normally, and their defect cannot be attributed to a lack of mlg-associated Igot/Ig/3 molecules. A novel functional assay for detecting antigenic peptides in subceUular fractions shows that wild-type mlg transfectants generate class II-peptide complexes intracellularly, whereas only free antigenic peptides are detectable in the mutant mlg transfectants. Furthermore, an antigen competition assay reveals that antigen internalized by the mutant mlgs fails to enter the intracellular processing compartment accessed by wild-type mlg. Therefore, mlg specifically targets bound and endocytosed antigen to the intracellular compartment where processed peptides associate with class II molecules, and the transmembrane Tyr5s7 residue plays an obligatory role in this process. Targeting of internalized antigen may be mediated by receptor-associated chaperones, and may be a general mechanism for optimizing the presentation of specifically bound and endocytosed antigens in B lymphocytes and other antigen-presenting cells. J. Exp.
Scandinavian Journal of Immunology, 1991
We do not agree with the analysis of Langman and Cohn on the function of Ig receptors. We have reviewed the available literature regarding anti-Ig activation of B cells and found it contradictory and unconvincing. We have presented experimental evidence on the inability of Ig receptors on B cells to mediate activation or tolerogenic signals. We suggest that the Ig receptors serve to focus antigen to specific B cells so the B cells can be activated by TI antigens or helper T cells. The Ig molecules also bind foreign antigen and thereby initiate internalization and antigen processing. The processed peptides are exported to the membrane, where they associate with MHC class II antigens, thus transforming B cells into efficient antigen-presenting cells.
Attachment of the antigen receptor to the B cell membrane
Immunochemistry
Models for the attachment of antigen receptors to the B cell membrane and some of the issues which arise on a consideration of this problem are discussed with reference to IgM receptors. It is suggested that the binding to the membrane may be a consequence of a unique structural feature of receptor immunoglobulin. Alternatively this may be a result of the subcellular site of biosynthesis of the receptor or the presence of a specific proreceptor molecule. Experiments to differentiate between the models are briefly discussed.
MHC class II antigen processing in B cells: Accelerated intracellular targeting of antigens
The Journal of Immunology
Processing and presentation by Ag-specific B cells is initiated by Ag binding to the B cell Ag receptor (BCR). Cross-linking of the BCR by Ag results in a rapid targeting of the BCR and bound Ag to the MHC class II peptide loading compartment (IIPLC). This accelerated delivery of Ag may be essential in vivo during periods of rapid Ag-driven B cell expansion and T cell-dependent selection. Here, we use both immunoelectron microscopy and a nondisruptive protein chemical polymerization method to define the intracellular pathway of the targeting of Ags by the BCR. We show that following cross-linking, the BCR is rapidly transported through transferrin receptor-containing early endosomes to a LAMP-1 ؉ , -hexosaminadase ؉ , multivesicular compartment that is an active site of peptide-class II complex assembly, containing both class II-invariant chain complexes in the process of invariant chain proteolytic removal as well as mature peptide-class II complexes. The BCR enters the class II-containing compartment as an intact mIg/Ig␣/Ig complex bound to Ag. The pathway by which the BCR targets Ag to the IIPLC appears not to be identical to that by which Ags taken up by fluid phase pinocytosis traffick, suggesting that the accelerated BCR pathway may be specialized and potentially independently regulated.
SpeculationAttachment of the antigen receptor to the B cel membrane
Immunochemistry, 1976
Models for the attachment of antigen receptors to the B cell membrane and some of the issues which arise on a consideration of this problem are discussed with reference to IgM receptors. It is suggested that the binding to the membrane may be a consequence of a unique structural feature of receptor immunoglobulin. Alternatively this may be a result of the subcellular site of biosynthesis of the receptor or the presence of a specific proreceptor molecule. Experiments to differentiate between the models are briefly discussed.