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

Research output: Contribution to journalArticle

Abstract

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
Volume204
Issue number12
DOIs
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. https://doi.org/10.4049/jimmunol.2000030