Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Effects of B cell–activating factor on tumor immunity
Mark Yarchoan, … , Todd D. Armstrong, Elizabeth M. Jaffee
Mark Yarchoan, … , Todd D. Armstrong, Elizabeth M. Jaffee
Published May 21, 2020
Citation Information: JCI Insight. 2020;5(10):e136417. https://doi.org/10.1172/jci.insight.136417.
View: Text | PDF
Research Article Immunology Oncology

Effects of B cell–activating factor on tumor immunity

  • Text
  • PDF
Abstract

Immunotherapies that modulate T cell function have been firmly established as a pillar of cancer therapy, whereas the potential for B cells in the antitumor immune response is less established. B cell–activating factor (BAFF) is a B cell–activating cytokine belonging to the TNF ligand family that has been associated with autoimmunity, but little is known about its effects on cancer immunity. We find that BAFF upregulates multiple B cell costimulatory molecules; augments IL-12a expression, consistent with Be-1 lineage commitment; and enhances B cell antigen-presentation to CD4+ Th cells in vitro. In a syngeneic mouse model of melanoma, BAFF upregulates B cell CD40 and PD-L1 expression; it also modulates T cell function through increased T cell activation and TH1 polarization, enhanced expression of the proinflammatory leukocyte trafficking chemokine CCR6, and promotion of a memory phenotype, leading to enhanced antitumor immunity. Similarly, adjuvant BAFF promotes a memory phenotype of T cells in vaccine-draining lymph nodes and augments the antitumor efficacy of whole cell vaccines. BAFF also has distinct immunoregulatory functions, promoting the expansion of CD4+Foxp3+ Tregs in the spleen and tumor microenvironment (TME). Human melanoma data from The Cancer Genome Atlas (TCGA) demonstrate that BAFF expression is positively associated with overall survival and a TH1/IFN-γ gene signature. These data support a potential role for BAFF signaling as a cancer immunotherapy.

Authors

Mark Yarchoan, Won Jin Ho, Aditya Mohan, Yajas Shah, Teena Vithayathil, James Leatherman, Lauren Dennison, Neeha Zaidi, Sudipto Ganguly, Skylar Woolman, Kayla Cruz, Todd D. Armstrong, Elizabeth M. Jaffee

×

Figure 1

BAFF upregulates multiple B cell costimulatory molecules in vitro and induces a Be-1 phenotype in B cells.

Options: View larger image (or click on image) Download as PowerPoint
BAFF upregulates multiple B cell costimulatory molecules in vitro and in...
(A) Treatment of isolated B cells with BAFF in vitro significantly upregulates the expression of CD21, CD23, CD40, CD5, CD80, CD86, ICOS-L, MHCII, and PD-L1 (n = 5 per group, 2-tailed unpaired t test, ***P < 0.001, ****P < 0.0001) (B) Representative histograms describing the increase in MFI of B cell costimulatory molecules. (C) Treatment of whole splenocytes with recombinant BAFF in vitro increases the number of living B cells without significantly affecting T cells (n = 5 per group, 2-tailed unpaired t test, ***P < 0.001) (D and E) Similarly, in vitro treatment with BAFF does not change the phenotype or exhaustion profile of isolated T cells cultured with BAFF, suggesting that the downstream consequences of BAFF stimulation are most pronounced on B cells (n = 5 per group). (F) Targeted gene expression analysis of isolated B cells cultured with or without BAFF for 48 hours showed that the expression of ICOSL, CD40, H2-DMB2, and H2-Aa were among the most differentially expressed genes with BAFF (n = 3 per group). Significance was determined by nSolver’s DE Call function and adjusted using the Benjamini-Yekutieli correction method. (G) BAFF leads to upregulation of IL-12a, suggesting enhanced B cell polarization toward a Be-1 phenotype, whereas expression of genes associated with a Be-2 or Breg phenotype were decreased with BAFF.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts