Molecular mechanisms of B cell antigen receptor trafficking.
B lymphocytes are among the most efficient cells of the immune system in capturing, processing, and presenting MHC class II restricted peptides to T cells. Antigen capture is essentially restricted by the specificity of the clonotypic antigen receptor expressed on each B lymphocyte. However, receptor recognition is only one factor determining whether an antigen is processed and presented. The context of antigen encounter is crucial. In particular, polyvalent arrays of repetitive epitopes, indicative of infection, accelerate the delivery of antigen to specialized processing compartments, and up-regulate the surface expression of MHC class II and co-stimulatory molecules such as B7. Recent studies have demonstrated that receptor-mediated signaling and receptor-facilitated peptide presentation to T cells are intimately related. For example, rapid sorting of endocytosed receptor complexes through early endosomes requires the activation of the tyrosine Syk. This proximal kinase initiates all BCR-dependent signaling pathways. Subsequent entry into the antigen-processing compartment requires the tyrosine phosphorylation of the BCR constituent Igalpha and direct recruitment of the linker protein BLNK. Signals from the BCR also regulate the biophysical and biochemical properties of the targeted antigen-processing compartments. These observations indicate that the activation and recruitment of signaling molecules by the BCR orchestrate a complex series of cellular responses that favor the presentation of even rare or low-affinity antigens if encountered in contexts indicative of infection. The requirement for BCR signaling provides possible mechanisms by which cognate B:T cell interactions can be controlled by the milieu in which antigen engagement occurs.
Clark
Marcus R
MR
University of Chicago, Section of Rheumatology, 5841 South Maryland Avenue, Chicago, Illinois 60637, USA. mclark@medicine.bsd.uchicago.edu
Massenburg
Don
D
Zhang
Miao
M
Siemasko
Karyn
K
D010455:Peptides / Q000378:metabolism; D021381:Protein Transport; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction
D010455:Peptides; D011947:Receptors, Antigen, B-Cell