T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance.
IgG2a is known to be the most efficient antibody isotype for viral clearance. Here, we demonstrate a unique pathway of B-cell activation, leading to IgG2a production, and involving synergistic stimulation via B-cell antigen receptors, toll-like receptor 7 (TLR7), and IFNγ receptors on B cells. This synergistic stimulation leads to induction of T-box transcription factor T-bet expression in B cells, which, in turn, drives expression of CD11b and CD11c on B cells. T-bet/CD11b/CD11c positive B cells appear during antiviral responses and produce high titers of antiviral IgG2a antibodies that are critical for efficient viral clearance. The results thus demonstrate a previously unknown role for T-bet expression in B cells during viral infections. Moreover, the appearance of T-bet(+) B cells during antiviral responses and during autoimmunity suggests a possible link between these two processes.
Howard Hughes Medical Institute, Denver, CO 80206, USA.
Kira
K
Rubtsova
Anatoly V
AV
Rubtsov
Linda F
LF
van Dyk
John W
JW
Kappler
Philippa
P
Marrack
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018142:Gammaherpesvirinae / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D060888:Real-Time Polymerase Chain Reaction; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology; D020825:T-Box Domain Proteins / Q000235:genetics / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000276:immunology; D000096743:Interferon gamma Receptor; D000098815:T-bet Transcription Factor
D017931:DNA Primers; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D017471:Receptors, Interferon; D020825:T-Box Domain Proteins; D051199:Toll-Like Receptor 7; D000096743:Interferon gamma Receptor; D000098815:T-bet Transcription Factor; C477038:Tlr7 protein, mouse
interferon gamma; virus