Zeng, Shijuan G. and Ghnewa, Yasmeen G. and O'Reilly, Vincent P. and Lyons, Victoria G. and Atzberger, Ann and Hogan, Andrew and Exley, Mark A. and Doherty, Derek G. (2013) Human Invariant NKT Cell Subsets Differentially Promote Differentiation, Antibody Production, and T Cell Stimulation by B Cells In Vitro. Journal of Immunology, 191 (4). pp. 1666-1676. ISSN 0022-1767

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Abstract

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+, CD8α+, and CD4−CD8α− 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 α-galactosylceramide. Additionally, CD4+ iNKT cells induced expansions of cells with phenotypes of regulatory B cells. When cocultured with α-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+, CD8α+, and DN iNKT cells can differentially promote and regulate the induction of Ab and T cell responses by B cells.

Item Type:	Article
Keywords:	Human Invariant; NKT Cell; Subsets; Differentially; Promote Differentiation; Antibody Production; T Cell Stimulation; B Cells; In Vitro;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	12430
Identification Number:	https://doi.org/10.4049/jimmunol.1202223
Depositing User:	Andrew Hogan
Date Deposited:	17 Feb 2020 15:52
Journal or Publication Title:	Journal of Immunology
Publisher:	American Association of Immunologists
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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