Human CD4&amp;lt;sup&amp;gt;-&amp;lt;/sup&amp;gt; CD8&amp;lt;sup&amp;gt;-&amp;lt;/sup&amp;gt; Invariant Natural Killer T Cells Promote IgG Secretion from B Cells Stimulated by Cross-Linking of Their Antigen Receptors

Tomomitsu Miyasaka,Yoshitsugu Miyazaki,Yasushi Uemura,Yukiko Akahori,Namiko Miyamura,Tian-Yi Liu,Yuki Kinjo,Yurie Watanabe,Kazuyoshi Kawakami,Keiko Ishii

doi:10.4236/wjv.2016.62005

Human CD4&lt;sup&gt;-&lt;/sup&gt; CD8&lt;sup&gt;-&lt;/sup&gt; Invariant Natural Killer T Cells Promote IgG Secretion from B Cells Stimulated by Cross-Linking of Their Antigen Receptors

Tomomitsu Miyasaka, Yoshitsugu Miyazaki + Show 8 more

Open Access

https://doi.org/10.4236/wjv.2016.62005

Copy DOI

Abstract

Immunoglobulin (Ig) M production can be induced by the interaction of thymus-independent type-2 (TI-2) antigen (Ag) with B cell Ag receptors (BCRs) without the involvement of conventional T cells; for IgG production through the same process, however, a second signal is required. Previous studies have reported that invariant natural killer T (iNKT) cells may be responsible for the second signal involved in IgG production. In the present study, we addressed whether human iNKT cells could participate in the production of Ig against TI-2 Ag in vitro. Two major distinct subsets of human iNKT cells, CD4+ CD8β- (CD4) and CD4- CD8β- [double negative (DN)] cells, were generated from peripheral blood monocytes from a healthy volunteer. BCR engagement, triggered by anti-IgM antibody stimulation, examined here as a model of BCR engagement triggered by TI-2 Ag, induced abundant IgM production by B cells. Both CD4 and DN iNKT cells reduced IgM production and conversely enhanced IgG production in a dose-dependent manner. In addition, IgG production by CD19+CD27- (naive) and CD19+CD27+ (memory) B cells was predominantly promoted by DNiNKT cells rather than CD4 iNKT cells; nevertheless, IgM production by both B cell subsets was similarly reduced by either subset of iNKT cells. These results suggest that the DN iNKT subsets may preferentially promote Ig class switching by B cells upon stimulation with TI-2 Ag.

Highlights

The main causative bacteria of invasive infection, including Streptococcus pneumoniae and Haemophilus influenzae, possess thick polysaccharide capsules which confer the ability to resist phagocytosis by polymorphonuclear leukocytes [1]
We found that co-culture with invariant natural killer T (iNKT) cells reduced IgM production but increased IgG production by B cells stimulated via cross-linking of B cell receptors (BCRs), and that this activity was higher in double negative (DN) iNKT cells than in CD4 iNKT cells
Human CD4+CD8− (CD4) and CD4−CD8− (DN) Vα24 iNKT Cells To investigate the functional differences between the human iNKT subsets in terms of immunoglobulin production against TI-2 Ags, we initially expanded α-GalCer-specific CD4 and DN iNKT cells separated from healthy individuals

Summary

Introduction

The main causative bacteria of invasive infection, including Streptococcus pneumoniae and Haemophilus influenzae, possess thick polysaccharide capsules which confer the ability to resist phagocytosis by polymorphonuclear leukocytes [1]. Immunoglobulins specific for these polysaccharide capsules enhances opsonophagocytic killing (OPK) activity, which plays an important role in host protection against infections caused by these encapsulated bacteria [2] [3]. Polysaccharide capsule, a thymus-independent type 2 (TI-2) antigen (Ag), has highly repetitive structures with simultaneous cross-linking of B cell receptors (BCRs) and induces B cell proliferation and IgM production [7]. IFN-γ induces T cell-independent IgG production in response to TI-2 Ag [8], as this cytokine triggers the secondary stimulatory signals for T cell-independent B cell activation and isotype switching to produce IgG [9] [10]

Methods

Results

Discussion

Conclusion