Antigen-B Cell Receptor Complexes Associate with Intracellular major histocompatibility complex (MHC) Class II...

Area of Science:

• Immunology
• Cell Biology

Background:

• Antigen-presenting cells (APCs), including dendritic cells and B cells, are crucial for T cell activation.
• B cells possess a unique B cell receptor (BCR) for antigen recognition and a distinct mechanism for MHC class II-restricted antigen presentation.
• BCR engagement and subsequent antigen processing lead to specific B cell activation patterns.

Purpose of the Study:

• To investigate the intracellular association of antigen-BCR complexes with MHC class II molecules in B cells.
• To determine the role of specific MHC class II conformers in presenting BCR-internalized antigens.

Main Methods:

• Combined biochemical assays and Förster Resonance Energy Transfer (FRET) imaging.
• Analysis of antigen-BCR complex internalization and association with intracellular MHC class II.
• Characterization of MHC class II conformer incorporation and peptide loading.

Main Results:

• Internalized antigen-BCR complexes were found to associate with intracellular MHC class II molecules in B cells.
• The M1-paired MHC class II conformer was selectively incorporated into these complexes.
• This conformer was preferentially loaded with peptides derived from BCR-internalized cognate antigen.

Conclusions:

• B cells utilize internalized antigen-BCR complexes to interact with intracellular MHC class II molecules, potentially defining a site for class II peptide acquisition.
• A selective role for the M1-paired class II conformer in presenting cognate antigen was revealed.
• These findings elucidate B cell mechanisms for controlling peptide loading onto MHC class II, focusing antibody responses on BCR-reactive antigens.