BACKGROUND: Transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) expression on B cells is upregulated by Toll-like receptor (TLR) 4. OBJECTIVE: We sought to examine whether TACI synergizes with TLR4 in driving immunoglobulin production by B cells and to examine the mechanism of this synergy. METHODS: Purified mouse naive B cells were stimulated with the TACI ligand a proliferation-inducing ligand (APRIL) and with suboptimal concentrations of the TLR4 ligand LPS in the presence or absence of IL-4. Immunoglobulin secretion was measured by means of ELISA. Surface IgG1-positive B cells and CD138+ plasmacytoid cells were enumerated by means of FACS. Expression of gamma1 and epsilon germline transcripts, activation-induced cytidine deaminase, and gamma1 and epsilon mature transcripts was measured by means of RT-PCR. RESULTS: APRIL synergized with LPS in driving B-cell proliferation and IgM, IgG1, IgG3, IgE, and IgA production. This was mediated by TACI because it was preserved in B-cell maturation antigen-/-, but not TACI-/-, B cells. APRIL and LPS synergized to promote isotype switching, as evidenced by increased expression of activation-induced cytidine deaminase and gamma1 and epsilon mature transcripts and generation of surface IgG1-positive cells. More importantly, APRIL and LPS strongly synergized to drive the plasma cell differentiation program, as evidenced by an increase in CD138+ cells and expression of B lymphocyte induced maturation protein-1 (Blimp-1), interferon regulatory factor-4 (IRF-4), and the spliced form of X-box binding protein-1 (XBP-1). TACI-/- mice had impaired IgM and IgG1 antibody responses to immunization, with a suboptimal dose of the type I T cell-independent antigen 2, 4, 6- Trinitrophenol (TNP)-LPS. CONCLUSIONS: These observations suggest that TACI cooperates with TLR4 to drive B-cell differentiation and immunoglobulin production in vitro and in vivo.
BACKGROUND:Transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) expression on B cells is upregulated by Toll-like receptor (TLR) 4. OBJECTIVE: We sought to examine whether TACI synergizes with TLR4 in driving immunoglobulin production by B cells and to examine the mechanism of this synergy. METHODS: Purified mouse naive B cells were stimulated with the TACI ligand a proliferation-inducing ligand (APRIL) and with suboptimal concentrations of the TLR4 ligand LPS in the presence or absence of IL-4. Immunoglobulin secretion was measured by means of ELISA. Surface IgG1-positive B cells and CD138+ plasmacytoid cells were enumerated by means of FACS. Expression of gamma1 and epsilon germline transcripts, activation-induced cytidine deaminase, and gamma1 and epsilon mature transcripts was measured by means of RT-PCR. RESULTS:APRIL synergized with LPS in driving B-cell proliferation and IgM, IgG1, IgG3, IgE, and IgA production. This was mediated by TACI because it was preserved in B-cell maturation antigen-/-, but not TACI-/-, B cells. APRIL and LPS synergized to promote isotype switching, as evidenced by increased expression of activation-induced cytidine deaminase and gamma1 and epsilon mature transcripts and generation of surface IgG1-positive cells. More importantly, APRIL and LPS strongly synergized to drive the plasma cell differentiation program, as evidenced by an increase in CD138+ cells and expression of B lymphocyte induced maturation protein-1 (Blimp-1), interferon regulatory factor-4 (IRF-4), and the spliced form of X-box binding protein-1 (XBP-1). TACI-/- mice had impaired IgM and IgG1 antibody responses to immunization, with a suboptimal dose of the type I T cell-independent antigen 2, 4, 6- Trinitrophenol (TNP)-LPS. CONCLUSIONS: These observations suggest that TACI cooperates with TLR4 to drive B-cell differentiation and immunoglobulin production in vitro and in vivo.
Authors: Mikhail B Litinskiy; Bernardetta Nardelli; David M Hilbert; Bing He; Andras Schaffer; Paolo Casali; Andrea Cerutti Journal: Nat Immunol Date: 2002-08-05 Impact factor: 25.606
Authors: M Yan; H Wang; B Chan; M Roose-Girma; S Erickson; T Baker; D Tumas; I S Grewal; V M Dixit Journal: Nat Immunol Date: 2001-07 Impact factor: 25.606
Authors: H Wang; S A Marsters; T Baker; B Chan; W P Lee; L Fu; D Tumas; M Yan; V M Dixit; A Ashkenazi; I S Grewal Journal: Nat Immunol Date: 2001-07 Impact factor: 25.606
Authors: Amaya I Wolf; Krystyna Mozdzanowska; William J Quinn; Michele Metzgar; Katie L Williams; Andrew J Caton; Eric Meffre; Richard J Bram; Loren D Erickson; David Allman; Michael P Cancro; Jan Erikson Journal: J Clin Invest Date: 2011-09-01 Impact factor: 14.808
Authors: Javier Chinen; Monica Martinez-Gallo; Wenli Gu; Montserrat Cols; Andrea Cerutti; Lin Radigan; Li Zhang; Lorraine Potocki; Marjorie Withers; James R Lupski; Charlotte Cunningham-Rundles Journal: J Allergy Clin Immunol Date: 2011-04-22 Impact factor: 10.793
Authors: Tanvi Arkatkar; Holly M Jacobs; Samuel W Du; Quan-Zhen Li; Kelly L Hudkins; Charles E Alpers; David J Rawlings; Shaun W Jackson Journal: Kidney Int Date: 2018-06-12 Impact factor: 10.612