# Embryonic origin and self-renewal of B-1a cells

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2020 · $371,795

## Abstract

PROJECT SUMMARY/ABSTRACT
 B-1 cells are murine innate immune B cells that preferentially localize in the peritoneal cavity, secrete
natural antibodies in a T cell independent manner, and play important roles in the first line of defense against
bacterial or viral infections, sepsis, and atherosclerosis. Despite the importance of B-1 cells in host defense
and homeostasis, their developmental origin is not clear. CD5+B-1a cells residing in the peritoneal cavity can
be reconstituted by transplantation of fetal liver (FL) progenitors, but not by adult bone marrow (BM)
hematopoietic stem cells (HSCs). Thus B-1a cells are considered to be of fetal origin and the mechanisms that
maintain B-1a cells in adult life without being replenished by adult HSCs have yet to be elucidated. The overall
goal of the project is to determine the contribution of HSC-independent embryonic B-1 progenitor cells into the
adult peritoneal B-1a cells and define the mechanisms that maintain B-1a cells throughout adult life.
 We have reported the presence of B-1 progenitor cells originated from hemogenic endothelial cells
(HECs) in the yolk sac (YS) in an HSC-deficient mouse model. Our recent preliminary data demonstrated that
fetal liver HSCs poorly reconstituted B-1a cells upon transplantation. Thus, we hypothesize that peritoneal B-
1a cells are derived from HECs and are totally independent of HSCs contributions at any stage of development
or adult life. In Aim 1, we will utilize a lineage tracing mouse model where one can mark HECs and their
progeny at a specific embryonic time point before HSC emergence by tamoxifen induction and we will
supplement this approach with HSC transplantation assays from fetus to neonatal and adult stages to prove
there is no contribution of HSCs into the B-1a cell pool. In Aim2, we will interrogate the molecular mechanisms
that maintain the self-replenishing ability of embryonic derived B-1a cells throughout life. Bmi1 is a polycomb
group protein that is critical for self-renewal of HSCs. We now report that the self-replenishing capacity of
Bmi1-/- and CD19Cre:Bmi1flox/flox B-1a cells is impaired, raising the hypothesis that Bmi1 plays an important role
in B-1a cell self-renewal. Since Bmi1-/- mice displayed a significantly more severe reduction in B-1a cell
number compared to CD19Cre:Bmi1flox/flox mice, we hypothesize that the B-1a cell microenvironment may be
altered in Bmi1-/- mice. We will examine a niche for B-1 cells, the recently reported fat-associated lymphoid
clusters (FALCs) in the omentum and mesentery, in Bmi1-/- mice. We will also pursue a downstream target of
Bmi1 as playing a role in B-1a self-renewal. These experiments consider cell intrinsic and extrinsic roles of
Bmi1 to define its critical role in B-1a cell maintenance and self-renewal. Our results will establish a new
paradigm for understanding B-1 cell development and maintenance in mice and will provide new tools to
translate to human investigation of B-1 like cells.
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## Key facts

- **NIH application ID:** 9939439
- **Project number:** 5R01AI121197-06
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Momoko Yoshimoto
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $371,795
- **Award type:** 5
- **Project period:** 2016-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939439

## Citation

> US National Institutes of Health, RePORTER application 9939439, Embryonic origin and self-renewal of B-1a cells (5R01AI121197-06). Retrieved via AI Analytics 2026-07-25 from https://api.ai-analytics.org/grant/nih/9939439. Licensed CC0.

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