IL-12 receptor β1 deficiency alters in vivo T follicular helper cell response in humans
Open Access
- 25 April 2013
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 121 (17), 3375-3385
- https://doi.org/10.1182/blood-2012-08-448902
Abstract
Antibody responses represent a key immune protection mechanism. T follicular helper (Tfh) cells are the major CD4+ T-cell subset that provides help to B cells to generate an antibody response. Tfh cells together with B cells form germinal centers (GCs), the site where high-affinity B cells are selected and differentiate into either memory B cells or long-lived plasma cells. We show here that interleukin-12 receptor β1 (IL-12Rβ1)–mediated signaling is important for in vivo Tfh response in humans. Although not prone to B cell-deficient–associated infections, subjects lacking functional IL-12Rβ1, a receptor for IL-12 and IL-23, displayed substantially less circulating memory Tfh and memory B cells than control subjects. GC formation in lymph nodes was also impaired in IL-12Rβ1–deficient subjects. Consistently, the avidity of tetanus toxoid–specific serum antibodies was substantially lower in these subjects than in age-matched controls. Tfh cells in tonsils from control individuals displayed the active form of signal transducer and activator of transcription 4 (STAT4), demonstrating that IL-12 is also acting on Tfh cells in GCs. Thus, our study shows that the IL-12–STAT4 axis is associated with the development and the functions of Tfh cells in vivo in humans.Keywords
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