Receptor-Facilitated Antigen Presentation Requires the Recruitment of B Cell Linker Protein to Ig1 (original) (raw)
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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.
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...
Structural compartmentalization of MHC class II signaling function
Immunology Today, 1993
Mutational analyses indicate that structural information necessary for these functions is compartmentalized in different aspects of the molecular complex. Here, William Wade and colleagues review the structual basis of this MHC class II function as defined in the I-Act and -[3 chains.
Germinal center entry not selection of B cells is controlled by peptide-MHCII complex density
Nature Communications
B cells expressing high affinity antigen receptors are advantaged in germinal centers (GC), perhaps by increased acquisition of antigen for presentation to follicular helper T cells and improved T-cell help. In this model for affinity-dependent selection, the density of peptide/ MHCII (pMHCII) complexes on GC B cells is the primary determinant of selection. Here we show in chimeric mice populated by B cells differing only in their capacity to express MHCII (MHCII +/+ and MHCII +/−) that GC selection is insensitive to halving pMHCII density. Alone, both B cell types generate identical humoral responses; in competition, MHCII +/+ B cells are preferentially recruited to early GCs but this advantage does not persist once GCs are established. During GC responses, competing MHCII +/+ and MHCII +/− GC B cells comparably accumulate mutations and have indistinguishable rates of affinity maturation. We conclude that B-cell selection by pMHCII density is stringent in the establishment of GCs, but relaxed during GC responses.
Seminars in Immunology, 1995
Nascent class II MHC (MHC class II) molecules are transported from the ER to a specialized late endocytic antigen processing compartment, termed MIIC (MHC class II compartment). This compartment, with some variations, has been defined in multiple studies of B cells, macrophages and dendritic cells. Though this compartment shares properties with both lysosomes and late endosomes, it is a specialized compartment that differs from these other endocytic compartments in important characteristics. The MIIC contains abundant MHC class II molecules and other molecules important for antigen processing, including lysosomal enzymes and HLA-DM. Biochemical and functional immunological assays have detected not only the presence but the initial formation of peptide-MHC class II complexes in MIIC during the processing of certain model antigens. However, MHC class II molecules are also present in other endocytic compartments, albeit at lower levels, and these compartments may also perform antigen processing functions.