• Home
  • Search Results
  • Increased T follicular helper cells and germinal center B cells are required for cGVHD and bronchiolitis obliterans.

Increased T follicular helper cells and germinal center B cells are required for cGVHD and bronchiolitis obliterans.

Blood (2014-05-14)
Ryan Flynn, Jing Du, Rachelle G Veenstra, Dawn K Reichenbach, Angela Panoskaltsis-Mortari, Patricia A Taylor, Gordon J Freeman, Jonathan S Serody, William J Murphy, David H Munn, Stefanie Sarantopoulos, Leo Luznik, Ivan Maillard, John Koreth, Corey Cutler, Robert J Soiffer, Joseph H Antin, Jerome Ritz, Jason A Dubovsky, John C Byrd, Kelli P MacDonald, Geoff R Hill, Bruce R Blazar
ABSTRACT

Chronic graft-versus-host disease (cGVHD) is a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Having shown that germinal center (GC) formation and immunoglobulin deposition are required for multiorgan system cGVHD and associated bronchiolitis obliterans syndrome (BOS) in a murine model, we hypothesized that T follicular helper (Tfh) cells are necessary for cGVHD by supporting GC formation and maintenance. We show that increased frequency of Tfh cells correlated with increased GC B cells, cGVHD, and BOS. Although administering a highly depletionary anti-CD20 monoclonal antibody (mAb) to mice with established cGVHD resulted in peripheral B-cell depletion, B cells remained in the lung, and BOS was not reversed. BOS could be treated by eliminating production of interleukin-21 (IL-21) by donor T cells or IL-21 receptor (IL-21R) signaling of donor B cells. Development of BOS was dependent upon T cells expressing the chemokine receptor CXCR5 to facilitate T-cell trafficking to secondary lymphoid organ follicles. Blocking mAbs for IL-21/IL-21R, inducible T-cell costimulator (ICOS)/ICOS ligand, and CD40L/CD40 hindered GC formation and cGVHD. These data provide novel insights into cGVHD pathogenesis, indicate a role for Tfh cells in these processes, and suggest a new line of therapy using mAbs targeting Tfh cells to reverse cGVHD.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acetone, ACS reagent, ≥99.5%
Sigma-Aldrich
Acetone, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%
Sigma-Aldrich
Acetone, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.5% (GC)
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Acetone, puriss., meets analytical specification of Ph. Eur., BP, NF, ≥99% (GC)
Sigma-Aldrich
Fluorescein isothiocyanate isomer I, suitable for protein labeling, ≥90% (HPLC), powder
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.8%
Supelco
Acetone, analytical standard
Sigma-Aldrich
Acetone, Laboratory Reagent, ≥99.5%
Sigma-Aldrich
Fluorescein 5(6)-isothiocyanate, BioReagent, suitable for fluorescence, mixture of 2 components, ≥90% (HPLC)
Supelco
Acetone, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Acetone, ACS reagent, ≥99.5%
Sigma-Aldrich
Fluorescein 5(6)-isothiocyanate, ≥90% (HPLC)
Sigma-Aldrich
Acetone, natural, ≥97%
Sigma-Aldrich
Acetone, histological grade, ≥99.5%
Sigma-Aldrich
Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)
Sigma-Aldrich
Acetone, suitable for HPLC, ≥99.9%
USP
Acetone, United States Pharmacopeia (USP) Reference Standard
Supelco
Acetone solution, certified reference material, 2000 μg/mL in methanol: water (9:1)
Sigma-Aldrich
Acetone, ≥99%, meets FCC analytical specifications
Sigma-Aldrich
Monoclonal Anti-Human IgM (μ-chain specific) antibody produced in mouse, clone MB-11, ascites fluid
Sigma-Aldrich
Anti-PD-1 (ab1) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Monoclonal Anti-PD-1 antibody produced in mouse, clone 7A11B1, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-CD4 antibody produced in rabbit, Ab1, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Fluorescein isothiocyanate isomer I, ≥97.5% (HPLC)
Sigma-Aldrich
Monoclonal Anti-Human IgM (μ-chain specific)−Alkaline Phosphatase antibody produced in mouse, clone MB-11, purified immunoglobulin, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-CD40 Ligand antibody produced in goat, affinity isolated antibody, lyophilized powder
Sigma-Aldrich
Anti-FCER2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
ANTI-IGHM(N-TERMINAL) antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Anti-CXCR5 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution

Social Media

LinkedIn icon
Twitter icon
Facebook Icon
Instagram Icon

MilliporeSigma

Research. Development. Production.

We are a leading supplier to the global Life Science industry with solutions and services for research, biotechnology development and production, and pharmaceutical drug therapy development and production.

© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.

Reproduction of any materials from the site is strictly forbidden without permission.