IL-12 receptor β1 deficiency alters in vivo T follicular helper cell response in humans.
Adolescent, Adult, Blotting, Western, Case-Control Studies, Child, Child, Preschool, Flow Cytometry, Fluorescent Antibody Technique, Germinal Center, Humans, Immunoenzyme Techniques, Immunologic Memory, Interleukin-12, Interleukin-23, Lymph Nodes, Palatine Tonsil, Phosphorylation, Plasma Cells, Receptors, Interleukin-12, STAT4 Transcription Factor, T-Lymphocyte Subsets, T-Lymphocytes, Helper-Inducer, Young Adult
Blood 2013 Apr 25; 121(17):3375-85
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. Blood 2013 Apr 25; 121(17):3375-85
Schmitt, Nathalie; Bustamante, Jacinta; Bourdery, Laure; Bentebibel, Salah Eddine; Boisson-Dupuis, Stephanie; Hamlin, Fran; Tran, Mau V; Blankenship, Derek; Pascual, Virginia; Savino, Daniel A; Banchereau, Jacques; Casanova, Jean-Laurent; and Ueno, Hideki, "IL-12 receptor β1 deficiency alters in vivo T follicular helper cell response in humans." (2013). Faculty Research 2013. 128.