TY - JOUR
T1 - IL-12 receptor b1 deficiency alters in vivo T follicular helper cell response in humans
AU - Schmitt, Nathalie
AU - Bustamante, Jacinta
AU - Bourdery, Laure
AU - Bentebibel, Salah Eddine
AU - Boisson-Dupuis, Stephanie
AU - Hamlin, Fran
AU - Tran, Mau V.
AU - Blankenship, Derek
AU - Pascual, Virginia
AU - Savino, Daniel A.
AU - Banchereau, Jacques
AU - Casanova, Jean Laurent
AU - Ueno, Hideki
N1 - Publisher Copyright:
© 2013 by The American Society of Hematology
PY - 2013/4/25
Y1 - 2013/4/25
N2 - Antibody responses represent a key immune protection mechanism. T follicular helper (Tfh) cells are the major CD41 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 b1 (IL-12Rb1)–mediated signaling is important for in vivo Tfh response in humans. Although not prone to B cell-deficient–associated infections, subjects lacking functional IL-12Rb1, 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-12Rb1–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.
AB - Antibody responses represent a key immune protection mechanism. T follicular helper (Tfh) cells are the major CD41 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 b1 (IL-12Rb1)–mediated signaling is important for in vivo Tfh response in humans. Although not prone to B cell-deficient–associated infections, subjects lacking functional IL-12Rb1, 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-12Rb1–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.
UR - http://www.scopus.com/inward/record.url?scp=84877332319&partnerID=8YFLogxK
U2 - 10.1182/blood-2012-08-448902
DO - 10.1182/blood-2012-08-448902
M3 - Article
C2 - 23476048
AN - SCOPUS:84877332319
SN - 0006-4971
VL - 121
SP - 3375
EP - 3385
JO - Blood
JF - Blood
IS - 17
ER -