Interleukin-6/STAT3 signaling regulates the ability of naive T cells to acquire B-cell help capacities.
The conditions leading to the activation/differentiation of T-helper (Th) cells dedicated for B-cell antibody production are still poorly characterized. We now demonstrate that interleukin-6 (IL-6) promotes the differentiation of naive T lymphocytes into helper cells able to promote B-cell activation and antibody secretion. IL-6-driven acquisition of B-cell help capacity requires expression of the signal transducer and activator of transcription 3 (STAT3), but not STAT4 or STAT6 transcription factors, suggesting that the ability to provide help to B cells is not restricted to a well-defined Th1 or Th2 effector population. T cell-specific STAT3-deficient mice displayed reduced humoral responses in vivo that could not be related to an altered expansion of CXCR5-expressing helper T cells. IL-6 was shown to promote IL-21 secretion, a cytokine that was similarly found to promote the differentiation of naive T cells into potent B-cell helper cells. Collectively, these data indicate that the ability to provide B-cell help is regulated by IL-6/IL-21 through STAT3 activation, independently of Th1, Th2, Th17, or follicular helper T cell (T(FH)) differentiation.
Eddahri
Fouad
F
Laboratoire de Physiologie Animale, Université Libre de Bruxelles, Brussels, Belgium.
Denanglaire
Sébastien
S
Bureau
Fabrice
F
Spolski
Rosanne
R
Leonard
Warren J
WJ
Leo
Oberdan
O
Andris
Fabienne
F
D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000235:genetics; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007378:Interleukins / Q000378:metabolism / Q000502:physiology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054380:Receptors, CXCR5 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000502:physiology*; D000098546:Interleukin-21
C513179:CXCR5 protein, mouse; D015850:Interleukin-6; D007378:Interleukins; D054380:Receptors, CXCR5; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D000098546:Interleukin-21