Decision criteria for resolving isotype switching conflicts by B cells.
Isotype switching by B cells is highly regulated by a group of cytokines including IL-4, IFN-gamma and TGF-beta. A B cell can only express one isotype at a time; however, during an immune response it may be exposed to combinations of stimuli that provide it with conflicting switching instructions. To determine how such cytokine-induced isotype switch conflicts would be resolved, the responses of B cells exposed to multiple cytokines were investigated. To eliminate complications arising from simultaneous effects of switching cytokines on proliferation, division number was used as a reference framework to monitor switching rate. The results show a clear hierarchy in which IFN-gamma is dominant over IL-4, and both IL-4 and IFN-gamma are dominant over TGF-beta. These studies reveal how B cells possess a set of logical decision criteria for dealing with pathogens that invoke a range of different stimuli.
Deenick
Elissa K
EK
Immune Regulation Group, Centenary Institute of Cancer Medicine and Cell Biology, Newtown, Australia.
Hasbold
Jhagvaral
J
Hodgkin
Philip D
PD
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*; D008297:Male; D051379:Mice; D016212:Transforming Growth Factor beta / Q000276:immunology*
D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma