B-cell-intrinsic STAT6 signaling controls germinal center formation.
Infection with helminths and exposure to antigens induce a strong type 2 immune response resulting in the secretion of the cytokines IL-4 and IL-13 by CD4(+) T cells and several innate cell types. IL-4 and IL-13 promote class switch recombination to IgG1 and IgE while their role for germinal center (GC) formation is poorly understood. We found a dramatic reduction in the numbers of GC B cells when investigating different type 2 immune responses in IL-4/IL-13-deficient mice. IL-4/IL-13 from T cells located outside B-cell follicles was sufficient for GC formation. We further revealed that IL-4/IL-13 acts directly on B cells for the formation of a robust GC response. The frequency of apoptotic GC B cells was not altered in the absence of IL-4/IL-13 and proliferation was even enhanced. However, deficiency of signal transducer and activator of transcription 6 signaling in B cells resulted in failure to downregulate the chemotactic receptor Gpr183 (Ebi2) and downregulation of this receptor has been shown to be essential for proper GC B-cell differentiation. Thus, T-cell-derived extrafollicular IL-4/IL-13 and signal transducer and activator of transcription 6-regulated genes in B cells play a critical role for orchestration of the GC response in type 2 immunity.
Department of Infection Biology, Institute for Clinical Microbiology, Immunology and Hygiene, Universitätsklinikum Erlangen and Friedrich-Alexander Universität, Erlangen-Nürnberg, Germany.
Adriana
A
Turqueti-Neves
Manuel
M
Otte
Olivia
O
Prazeres da Costa
Uta E
UE
Höpken
Martin
M
Lipp
Thorsten
T
Buch
David
D
Voehringer
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D018858:Germinal Center / Q000502:physiology*; D018793:Interleukin-13 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D050800:STAT6 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D018793:Interleukin-13; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015847:Interleukin-4
B cells; Germinal center; IL-13; IL-4; STAT6