Author(s)

Tomomitsu Miyasaka¹, Yurie Watanabe¹, Yukiko Akahori¹, Namiko Miyamura¹, Keiko Ishii¹, Yuki Kinjo², Yoshitsugu Miyazaki², Tian-Yi Liu^3,4, Yasushi Uemura^3,5, Kazuyoshi Kawakami^1*

¹Department of Medical Microbiology, Mycology and Immunology, Tohoku University Graduate School of Medicine, Sendai, Japan.
²Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, Tokyo, Japan.
³Division of Immunology, Aichi Cancer Center Research Institute (ACCRI), Nagoya, Japan.
⁴Key Laboratory of Cancer Center, Chinese PLA General Hospital, Beijing, China.
⁵Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center (NCC), Kashiwa, Japan.

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^- (naïve) 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.

Invariant Natural Killer T Cells, TI-2 Antigen, B Cells, IgM, IgG

Miyasaka, T. , Watanabe, Y. , Akahori, Y. , Miyamura, N. , Ishii, K. , Kinjo, Y. , Miyazaki, Y. , Liu, T. , Uemura, Y. and Kawakami, K. (2016) Human CD4^- CD8^- Invariant Natural Killer T Cells Promote IgG Secretion from B Cells Stimulated by Cross-Linking of Their Antigen Receptors. World Journal of Vaccines, 6, 34-41. doi: 10.4236/wjv.2016.62005.