Antigen affinity discrimination is an intrinsic function of the B cell receptor

• Published in: The Journal of experimental medicine Vol. 207; no. 5; pp. 1095 - 1111
• Main Authors: Liu, Wanli, Meckel, Tobias, Tolar, Pavel, Sohn, Hae Won, Pierce, Susan K
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 10.05.2010
• Subjects: Animals; Antibody Formation - immunology; Antigen Presentation - immunology; B-Lymphocyte Subsets - immunology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Lipid Bilayers - immunology; Lymphocyte Activation - immunology; Mice; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - physiology; Receptors, IgG - immunology; Signal Transduction - immunology; Signal Transduction - physiology
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.20092123

Antibody affinity maturation, a hallmark of adaptive immune responses, results from the selection of B cells expressing somatically hypermutated B cell receptors (BCRs) with increased affinity for antigens. Despite the central role of affinity maturation in antibody responses, the molecular mechanisms by which the increased affinity of a B cell for antigen is translated into a selective advantage for that B cell in immune responses is incompletely understood. We use high resolution live-cell imaging to provide evidence that the earliest BCR-intrinsic events that follow within seconds of BCR-antigen binding are highly sensitive to the affinity of the BCR for antigen. High affinity BCRs readily form oligomers and the resulting microclusters grow rapidly, resulting in enhanced recruitment of Syk kinase and calcium fluxes. Thus, B cells are able to read the affinity of antigen by BCR-intrinsic mechanisms during the earliest phases of BCR clustering, leading to the initiation of B cell responses.