Peer-Reviewed Journal Details
Mandatory Fields
Zeng, SG;Ghnewa, YG;O'Reilly, VP;Lyons, VG;Atzberger, A;Hogan, AE;Exley, MA;Doherty, DG
2013
August
Journal of Immunology
Human Invariant NKT Cell Subsets Differentially Promote Differentiation, Antibody Production, and T Cell Stimulation by B Cells In Vitro
Published
14 ()
Optional Fields
ANTIGEN-PRESENTING CELLS ALPHA-GALACTOSYLCERAMIDE CUTTING EDGE HUMORAL IMMUNITY DENDRITIC CELLS COGNATE HELP ACTIVATION RESPONSES CD1D INDUCTION
191
1666
1676
Invariant NK T (iNKT) cells can provide help for B cell activation and Ab production. Because B cells are also capable of cytokine production, Ag presentation, and T cell activation, we hypothesized that iNKT cells will also influence these activities. Furthermore, subsets of iNKT cells based on CD4 and CD8 expression that have distinct functional activities may differentially affect B cell functions. We investigated the effects of coculturing expanded human CD4(+), CD8 alpha(+), and CD4(-) CD8 alpha(-) double-negative (DN) iNKT cells with autologous peripheral B cells in vitro. All iNKT cell subsets induced IgM, IgA, and IgG release by B cells without needing the iNKT cell agonist ligand alpha-galactosylceramide. Additionally, CD4(+) iNKT cells induced expansions of cells with phenotypes of regulatory B cells. When cocultured with alpha-galactosylceramide-pulsed B cells, CD4(+) and DN iNKT cells secreted Th1 and Th2 cytokines but at 10-1000-fold lower levels than when cultured with dendritic cells. CD4(+) iNKT cells reciprocally induced IL-4 and IL-10 production by B cells. DN iNKT cells expressed the cytotoxic degranulation marker CD107a upon exposure to B cells. Remarkably, whereas iNKT cell subsets could induce CD40 and CD86 expression by B cells, iNKT cell-matured B cells were unable to drive proliferation of autologous and alloreactive conventional T cells, as seen with B cells cultured in the absence of iNKT cells. Therefore, human CD4(+), CD8 alpha(+), and DN iNKT cells can differentially promote and regulate the induction of Ab and T cell responses by B cells.
BETHESDA
0022-1767
10.4049/jimmunol.1202223
Grant Details