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B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways.

Publication ,  Journal Article
Allen, JL; Fore, MS; Wooten, J; Roehrs, PA; Bhuiya, NS; Hoffert, T; Sharf, A; Deal, AM; Armistead, P; Coghill, J; Gabriel, DA; Irons, R ...
Published in: Blood
September 20, 2012

Recent data reveal an important role for B cells in the pathogenesis of chronic GVHD (cGVHD). Patients with cGVHD have delayed B-cell reconstitution and elevated BAFF to B-cell ratios compared to patients without cGVHD. The mechanisms promoting and sustaining B-cell activation in this disease, however, remain unknown. As BAFF increases murine B-cell metabolism and survival and maintains autoreactive B-cell clones, we performed ex vivo analyses of peripheral B cells from 51 patients who either had or did not have active cGVHD and were greater than 1 year from the time of allogeneic hematopoietic stem cell transplantation. We found that B cells from patients with active cGVHD were in a heightened metabolic state and were resistant to apoptosis. Exogenous BAFF treatment amplified cell size and survival in B cells from these patients. We found significantly increased signaling through ERK and AKT that associated with decreased levels of proapoptotic Bim, suggesting a mechanistic link between elevated BAFF levels and aberrant B-cell survival. Thus, we identify a role for BAFF in the pathogenesis of cGVHD and define B-cell activation and survival pathways suitable for novel therapeutic development in cGVHD.

Duke Scholars

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Published In

Blood

DOI

EISSN

1528-0020

Publication Date

September 20, 2012

Volume

120

Issue

12

Start / End Page

2529 / 2536

Location

United States

Related Subject Headings

  • Young Adult
  • Transplantation, Homologous
  • Signal Transduction
  • Middle Aged
  • Male
  • Lymphocyte Activation
  • Immunology
  • Immunoblotting
  • Humans
  • Hematopoietic Stem Cell Transplantation
 

Citation

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Allen, J. L., Fore, M. S., Wooten, J., Roehrs, P. A., Bhuiya, N. S., Hoffert, T., … Sarantopoulos, S. (2012). B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways. Blood, 120(12), 2529–2536. https://doi.org/10.1182/blood-2012-06-438911
Allen, Jessica L., Matthew S. Fore, Jenna Wooten, Philip A. Roehrs, Nazmim S. Bhuiya, Todd Hoffert, Andrew Sharf, et al. “B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways.Blood 120, no. 12 (September 20, 2012): 2529–36. https://doi.org/10.1182/blood-2012-06-438911.
Allen JL, Fore MS, Wooten J, Roehrs PA, Bhuiya NS, Hoffert T, et al. B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways. Blood. 2012 Sep 20;120(12):2529–36.
Allen, Jessica L., et al. “B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways.Blood, vol. 120, no. 12, Sept. 2012, pp. 2529–36. Pubmed, doi:10.1182/blood-2012-06-438911.
Allen JL, Fore MS, Wooten J, Roehrs PA, Bhuiya NS, Hoffert T, Sharf A, Deal AM, Armistead P, Coghill J, Gabriel DA, Irons R, Essenmacher A, Shea TC, Richards K, Cutler C, Ritz J, Serody J, Baldwin AS, Sarantopoulos S. B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways. Blood. 2012 Sep 20;120(12):2529–2536.

Published In

Blood

DOI

EISSN

1528-0020

Publication Date

September 20, 2012

Volume

120

Issue

12

Start / End Page

2529 / 2536

Location

United States

Related Subject Headings

  • Young Adult
  • Transplantation, Homologous
  • Signal Transduction
  • Middle Aged
  • Male
  • Lymphocyte Activation
  • Immunology
  • Immunoblotting
  • Humans
  • Hematopoietic Stem Cell Transplantation