Bmi1 maintains the self-renewal property of innate-like B lymphocytes

Michihiro Kobayashi, Yang Lin, Akansha Mishra, Chris Shelly, Rui Gao, Colton W. Reeh, Paul Zhiping Wang, Rongwen Xi, Yunlong Liu, Pamela Wenzel, Eliver Ghosn, Yan Liu, Momoko Yoshimoto

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The self-renewal ability is a unique property of fetal-derived innate-like B-1a lymphocytes, which survive and function without being replenished by bone marrow (BM) progenitors. However, the mechanism by which IgM-secreting mature B-1a lymphocytes self-renew is poorly understood. In this study, we showed that Bmi1 was critically involved in this process. Although Bmi1 is considered essential for lymphopoiesis, the number of mature conventional B cells was not altered when Bmi1 was deleted in the B cell lineage. In contrast, the number of peritoneal B-1a cells was significantly reduced. Peritoneal cell transfer assays revealed diminished self-renewal ability of Bmi1-deleted B-1a cells, which was restored by additional deletion of Ink4-Arf, the well-known target of Bmi1. Fetal liver cells with B cell-specific Bmi1 deletion failed to repopulate peritoneal B-1a cells, but not other B- 2 lymphocytes after transplantation assays, suggesting that Bmi1 may be involved in the developmental process of B-1 progenitors to mature B-1a cells. Although Bmi1 deletion has also been shown to alter the microenvironment for hematopoietic stem cells, fatassociated lymphoid clusters, the reported niche for B-1a cells, were not impaired in Bmi1-/- mice. RNA expression profiling suggested lysine demethylase 5B (Kdm5b) as another possible target of Bmi1, which was elevated in Bmi1-/- B-1a cells in a stress setting and might repress B-1a cell proliferation. Our work has indicated that Bmi1 plays pivotal roles in self-renewal and maintenance of fetal-derived B-1a cells.

Original languageEnglish (US)
Pages (from-to)3262-3272
Number of pages11
JournalJournal of Immunology
Issue number12
StatePublished - Jun 15 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Kobayashi, M., Lin, Y., Mishra, A., Shelly, C., Gao, R., Reeh, C. W., Wang, P. Z., Xi, R., Liu, Y., Wenzel, P., Ghosn, E., Liu, Y., & Yoshimoto, M. (2020). Bmi1 maintains the self-renewal property of innate-like B lymphocytes. Journal of Immunology, 204(12), 3262-3272.