B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase

doi:10.1073/pnas.0914347107

B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase

^aImmunotherapy and Cancer Centers, Departments of
^bPathology and
^cMedicine, and
^dFlow Cytometry Core Facility, Medical College of Georgia, Augusta, GA 30912;
^e Research Institute of Molecular Pathology, A-1030 Vienna, Austria; and
^fDepartment of Pediatrics, Medical College of Georgia, Augusta, GA 30912

↵ ¹Present address: The New York Stem Cell Foundation, New York, NY 10023.

Edited* by Rafi Ahmed, Emory University, Atlanta, GA, and approved April 27, 2010 (received for review December 14, 2009)

Abstract

A discrete population of splenocytes with attributes of dendritic cells (DCs) and coexpressing the B-cell marker CD19 is uniquely competent to express the T-cell regulatory enzyme indoleamine 2,3-dioxygenase (IDO) in mice treated with TLR9 ligands (CpGs). Here we show that IDO-competent cells express the B-lineage commitment factor Pax5 and surface immunoglobulins. CD19 ablation abrogated IDO-dependent T-cell suppression by DCs, even though cells with phenotypic attributes matching IDO-competent cells developed normally and expressed IDO in response to interferon γ. Consequently, DCs and regulatory T cells (Tregs) did not acquire T-cell regulatory functions after TLR9 ligation, providing an alternative perspective on the known T-cell regulatory defects of CD19-deficient mice. DCs from B-cell–deficient mice expressed IDO and mediated T-cell suppression after TLR9 ligation, indicating that B-cell attributes were not essential for B-lymphoid IDO-competent cells to regulate T cells. Thus, IDO-competent cells constitute a distinctive B-lymphoid cell type with quintessential T-cell regulatory attributes and phenotypic features of both B cells and DCs.

Footnotes

²To whom correspondence should be addressed. E-mail: amellor{at}mcg.edu.
Author contributions: B.A.J., M.B., D.H.M., and A.L.M. designed research; B.A.J., D.J.K., B.B., P.R.C., B.K., and B.V. performed research; B.B., M.S., P.A.K., J.P., B.V., M.B., D.H.M., and A.L.M. contributed new reagents/analytic tools; B.A.J., D.J.K., B.B., P.R.C., B.K., B.V., M.B., D.H.M., and A.L.M. analyzed data; and B.A.J. and A.L.M. wrote the paper.
↵*This Direct Submission article had a prearranged editor.
Conflict of interest statement: D.H.M. and A.L.M. receive consulting income and research support from NewLink Genetics Inc., which has licensed patent rights based on intellectual property emanating from their laboratories.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.0914347107/-/DCSupplemental.