Stability of the B cell antigen receptor modulates its signaling and antigen-targeting functions.
The binding of antigens to the B cell antigen receptor (BCR) results in the initiation of signaling cascades and the internalization of the antigens for processing and presentation. Recent studies indicate that antigen binding destabilizes the BCR as a mechanism to down-regulate B cell responses. Two point mutations in the transmembrane domain of murine membrane IgM (mIgM) (YS to VV) weaken the interaction of mIgM with Igalpha/Igbeta heterodimer, resulting in a destabilized BCR. Using muYS/VV BCR, effects of the destabilized BCR on the functions of an endogenous wild-type mIgG(2a) BCR were analyzed. The muYS/VV BCR is defective in signaling and does not target antigens to late endocytic compartments for processing and presentation. Coligation of the muYS/VV BCR with the endogenous BCR interferes with antigen-targeting functions of the endogenous BCR. Thus, the destabilized BCR has a dominant effect, down-regulating the function of stable wild-type BCR. The ability of the destabilized BCR to influence the stable BCR may play an important role in turning off B cell responses for antigen-driven anergy and tolerance.
Parent
Beth A
BA
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA.
Wang
Xiaoxia
X
Song
Wenxia
W
D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D003432:Cross-Linking Reagents; D011992:Endosomes / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology*; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000276:immunology*; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins / Q000276:immunology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D015703:Antigens, CD; D003432:Cross-Linking Reagents; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine