# Regulation of antibody secreting cell (ASC) homeostasis by Ufbp1.

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2022 · $451,804

## Abstract

Secreted antibodies play an important role in the neutralization of pathogens and the protection of host.
Two types of ASCs develop during B cell responses: short lived plasmablasts (PBs) and long-lived plasma
cells (PCs). In secondary lymphoid organs, antigen-activated B cells differentiate into PBs. Some of these
PBs home to bone marrow, where they differentiate into long-lived PCs. In bone marrow, PCs persist from
a few months to years and secrete copious amounts of high-affinity antibodies which are central to the
neutralization of pathogens. Therefore, understanding the molecular mechanisms underlying the
development, survival and function of plasma cells is critical to designing better vaccines to generate
effective immune responses. Ufm1 (ubiquitin-fold modifier 1) is a ubiquitin-like polypeptide that is post-
translationally conjugated to target proteins via the ufmylation process and thereby modifies their function.
Ufm1 binding protein (Ufbp1 or DDGRK1) is the first identified target of the ufmylation pathway. Ufl1 is
the E3 ligase that attaches Ufm1 to Ufbp1. We published a novel role of Ufbp1 in development and function
of ASCs. Consistent with this, mice lacking Ufbp1 in B cells have significantly reduced amounts of serum
immunoglobulins and mount a highly defective antibody response against antigens. Aim 1 will use
structure-function analysis to identify the regions of Ufbp1 that differentially regulate development of ASC
and helps them to acquire the ability to produce antibodies. Aim 2 will test the roles of Ufm1 and Ufl1
pathway in development and function of ASCs. Aim3 will test the role of Ufbp1, Ufl1 and Ufm1 in promoting
survival of long-lived PCs, maintaining their functionality and underlying molecular mechanisms. The
outcome of the proposed study will provide an understanding of a novel molecular mechanism underlying
Ufbp1-mediated promotion of antibody response and could potentially help in designing better vaccines
and treatments for pathologies related to antibody secreting cells.

## Key facts

- **NIH application ID:** 10469611
- **Project number:** 5R01AI155774-03
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Nagendra Singh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $451,804
- **Award type:** 5
- **Project period:** 2020-09-24 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469611

## Citation

> US National Institutes of Health, RePORTER application 10469611, Regulation of antibody secreting cell (ASC) homeostasis by Ufbp1. (5R01AI155774-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10469611. Licensed CC0.

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