Identification of human B-1 helper T cells with a Th1-like memory phenotype and high integrin CD49d expression

Jae Ghi Lee, Joon Young Jang, Taishi Fang, Yixuan Xu, Ji Jing Yan, Jung Hwa Ryu, Hee Jung Jeon, Tai Yeon Koo, Dong Ki Kim, Kook Hwan Oh, Tae Jin Kim, Jaeseok Yang

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8 Scopus citations


Human B-1 cells have been proposed to be CD20+CD27+CD43+CD1c- B cells found in the umbilical cord and adult peripheral blood, but their regulatory mechanisms have not been well elucidated. Previously, we reported that mouse CD49dhigh CD4+ T cells could enhance the secretion of natural antibodies by B-1 cells. In this study, we aimed to investigate the presence and helper functions of the human equivalents of murine CD49dhigh CD4+ T cells. Here, we showed that human CD49dhigh CD4+ T cells found in the peritoneal cavity (PEC), spleen, and peripheral blood can enhance the production of IgM antibodies by B-1 cells. As revealed in mouse, CD49dhigh CD4+ T cells were more abundant in the PEC and showed a higher tendency to form conjugates with B cells than CD49dlow CD4+ T cells. Moreover, CD49dhigh CD4+ T cells showed a Th1-like memory phenotype, characterized by high expression of CD44 and CXCR3; low expression of CD62L and CCR7; rapid production of IFN-γ, tumor necrosis factor-α, and IL-2 upon stimulation with phorbol myristate acetate and ionomycin; and rapid proliferation upon stimulation with anti-CD3 and anti-CD28 antibodies. These cells also expressed high levels of PD-1, ICOS, and CD5, suggesting that they are undergoing chronic stimulation. Remarkably, CD49dhigh CD4+ T cells specifically helped B-1 cells, but not follicular memory B cells (CD27+ CD43-CD1c-) or marginal zone B cells (CD27+CD43-CD1c+), produce IgM and IgG antibodies. In parallel, the titer of human anti-blood group A IgM was positively correlated with the frequency of CD49dhigh CD4+ T cells. In conclusion, we identified human CD49dhigh CD4+ T cells with a Th1-like memory phenotype that secrete Th1 proinflammatory cytokines and help B-1 cells secrete antibodies, thereby aiding in primary defense. We suggest that these CD49dhigh CD4+ T cells are a unique type of B-cell helper T cells distinct from follicular helper T cells.

Original languageEnglish
Article number1617
JournalFrontiers in Immunology
Issue numberJUL
StatePublished - 16 Jul 2018

Bibliographical note

Funding Information:
This research was supported by the Bio and Medical Technology Development Program of the NRF funded by the Ministry of Science and ICT (grant NRF-2015M3A9D3051413) and Basic Science Research Program of the NRF funded by the Ministry of Education (NRF-2016R1A6A3A01010976).

Publisher Copyright:
© 2018 Lee, Jang, Fang, Xu, Yan, Ryu, Jeon, Koo, Kim, Oh, Kim and Yang.


  • Antibody
  • B-1 cell
  • CD49d
  • Helper T cell
  • Memory phenotype
  • Th1


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