Augmentation of signaling through BCR containing IgE but not that containing IgA due to lack of CD22-mediated signal regulation.
The B cell membrane molecules CD22 and CD72 contain ITIMs in their cytoplasmic portion, and negatively regulate signaling through BCR. Various lines of evidence suggest that ligation of BCR containing IgG (IgG-BCR) transmits augmented signaling due to lack of CD22-mediated signal regulation. However, the signaling capacities of BCR containing IgA and IgE remain largely undefined. In this study, we demonstrate that both IgE-BCR and IgG-BCR, but not IgA-BCR, transmit augmented signaling compared with IgM-BCR. Ligation of IgE-BCR does not induce signaling events required for CD22-mediated signal inhibition, and restoration of these signaling events by coligation of CD22 with BCR abrogates signal augmentation. Furthermore, the cytoplasmic portion of IgE but not that of IgA is sufficient for suppressing CD22-mediated signal inhibition. These findings strongly suggest that the cytoplasmic portion of IgE but not that of IgA reverses CD22-mediated signal inhibition, leading to augmentation of signaling through IgE-BCR but not IgA-BCR. Augmented IgE-BCR signaling appears to play a role in production of large amounts of IgE during helminth infection, whereas regulated signaling through IgA-BCR may be crucial for constitutive production of IgA for mucosal immunity.
Sato
Motohiko
M
Laboratory of Immunology, School of Biomedical Science, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
Adachi
Takahiro
T
Tsubata
Takeshi
T
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D006373:Helminthiasis / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology*; D007070:Immunoglobulin A / Q000276:immunology*; D007073:Immunoglobulin E / Q000276:immunology*; D007152:Immunologic Capping / Q000276:immunology; D051379:Mice; D051562:Proto-Oncogene Proteins c-bcr / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C513972:CD72 antigen, mouse; C497868:Cd22 protein, mouse; D007070:Immunoglobulin A; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D007073:Immunoglobulin E; C496614:Bcr protein, mouse; D051562:Proto-Oncogene Proteins c-bcr