Intrinsic properties of immunoglobulin IgG1 isotype-switched B cell receptors promote microclustering and the initiation of signaling.
Memory B cells express high-affinity, immunoglobulin GB cell receptors (IgG BCRs) that enhance B cell responses, giving rise to the rapid production of high-affinity, IgG antibodies. Despite the central role of IgG BCRs in memory responses, the mechanisms by which the IgG BCRs function to enhance B cell responses are not fully understood. Using high-resolution live-cell imaging, we showed that IgG1 BCRs dramatically enhanced the earliest BCR-intrinsic events that followed within seconds of B cells' encounter with membrane bound antigen, including BCR oligomerization and BCR microcluster growth, leading to Syk kinase recruitment and calcium responses. The enhancement of these early events was dependent on a membrane proximal region of the IgG1 cytoplasmic tail not previously appreciated to play a role in IgG1 BCR signaling. Thus, intrinsic properties of the IgG1 BCR enhance early antigen-driven events that ultimately translate into heightened signaling.
Liu
Wanli
W
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA.
Meckel
Tobias
T
Tolar
Pavel
P
Sohn
Hae Won
HW
Pierce
Susan K
SK
D000818:Animals; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D014162:Transfection
D007074:Immunoglobulin G; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D002118:Calcium