# Pilot Project-Characterization of antigen presentation by ABCs

> **NIH NIH U19** · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · 2024 · $334,896

## Abstract

Pilot Project Summary/Abstract
 SLE is a systemic autoimmune disease in which B cells have a major role in pathogenesis. Recent
studies identified a non-classical subset of B cells, named age-associated B cells (ABCs), which is expanded
in inflammatory diseases such as SLE. In SLE patients, expansion of ABCs is more evident in those with lupus
nephritis (LN) and with high titers of autoantibodies. Functionally, ABCs produce autoantibodies following ex
vivo stimulation with a toll-like receptor (TLR) 7/8 agonist and cytokines. ABCs also display features of
professional antigen presenting cells (APCs) with higher expression of MHC II and co-stimulatory molecules
than what is observed in other B cell subsets. In mice, inhibition of ABC generation alleviated lupus
manifestation mediated, in part, by prevention of effector T cell differentiation, especially follicular helper T
(Tfh) cells. While these observations support the contribution of ABCs to SLE pathogenesis, significant gaps in
knowledge exist regarding their pathogenic function.
 Our laboratory and others found that ABCs are a metabolically and transcriptionally distinct B cell
population compared to naïve or memory B cells. ABCs produce higher levels of proinflammatory cytokines,
including IL-6, IL-10 and IL-1β, and exhibit inflammasome formation. ABCs can uptake soluble antigens
through B cell receptor-independent manner. We also observed expression of HIF1A in ABCs. An
inflammatory function of HIF1A has been identified in myeloid cells, but not in B cells.
 The pilot project will characterize the function of ABCs as antigen presenting cells (APCs). There is the
potential to relate this phenotypic characterization of ABCs to the ANA response studied in the Principal
Project. Single cell analyses will also be available from patients with active SLE and pre-flare samples; this
data will be generated by the Collaborative Project. The pilot project will benefit from the infrastructure of the
ACE project and will use B cells derived from patients being studied in the cohorts available through the
Collaborative Project.

## Key facts

- **NIH application ID:** 10844199
- **Project number:** 2U19AI144306-06
- **Recipient organization:** FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** Sun Jung Kim
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $334,896
- **Award type:** 2
- **Project period:** 2019-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10844199

## Citation

> US National Institutes of Health, RePORTER application 10844199, Pilot Project-Characterization of antigen presentation by ABCs (2U19AI144306-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10844199. Licensed CC0.

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