Research on Short-Lived and Long-Lived Plasma Cells in Humans

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Topic Description

Post Date: September 10, 2025

Expiration Date: September 10, 2026

Purpose

This topic encourages applications to understand the biology of Short-Lived Plasma Cells (SLPC) and Long-Lived Plasma Cells (LLPC) through characterization of plasma cell phenotypes and function in human health and disease.

Background

The continuous production of antibodies by LLPC is critical for life-long protective humoral immunity because it does not require restimulation with antigen, unlike the requirements to activate memory B cells. However, LLPC also produce antibodies that: 

  • Mediate some autoimmune diseases
  • Promote allergic responses
  • Mediate organ/tissue transplant rejection
  • Limit patient access to organ transplantation via pre-sensitization 

LLPC cannot be easily depleted by most drugs currently used to deplete B cells. In contrast, SLPC have reduced survival programming, generally produce lower affinity antibodies, and are susceptible to B cell depletion therapies. LLPC may arise from a subset of SLPC or from distinct differentiation pathways compared to SLPC; although details of the pathways, mediators, and mechanisms of SLPC and LLPC generation remain to be elucidated.

This topic encourages applications that include:

  • Ex vivo analysis of human samples
  • New approach methodologies (NAMs)
  • Computational modeling of plasma cells in human health and disease

 

Central Scientific Contact:
Moriah Castleman, Ph.D.
[email protected]

Participating ICOs

National Institute of Allergy and Infectious Diseases (NIAID)

This topic will provide foundational information for rational vaccine design to promote Long-Lived Plasma Cells (LLPC) for durable immunity; diminish LLPC or their activity in autoimmune and allergic diseases, and organ transplantation; or redirect plasma cell fate differentiation to the Short-Lived Plasma Cell (SLPC) population. 

Examples of research areas associated with protective or pathogenic immune responses in infectious, immune-mediated or allergic diseases include:

  • Identification/characterization of precursor subsets of SLPC or LLPC.
  • Characterization of tissue sites and local factors that promote bone marrow engraftment, differentiation, and persistence or residence at alternative sites, e.g., mucosa.
  • Effects of host factors (age, microbiome, etc) on SLPC and LLPC differentiation and function.
  • Comparison of antigen types and formats (soluble, membrane bound) promoting LLPC vs SLPC.
ICO Scientific Contact:
Moriah Castleman, Ph.D.
[email protected]

National Institute on Aging (NIA)

Examples of research areas relevant to the National Institute on Aging (NIA): 

  • Changes in the biology of plasma cell subpopulations during aging.
  • Functional impact of aging phenotypes such as cardiac amyloidosis, frailty, and cognitive decline in plasma cell disorders.
  • Geroscience interventions to enhance effective immune response, delay or potentially reverse immune aging in patients with plasma cell disorders.
ICO Scientific Contact:
Hongwei Gao, M.D., Ph.D.
[email protected]

Mulualem E. Tilahun, D.V.M., Ph.D.
[email protected]

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ICO Scientific Contact:
Marie Mancini, Ph.D.
[email protected]

Office of Research on Women's Health (ORWH)

The Office of Autoimmune Disease Research in the Office of Research on Women’s Health (OADR-ORWH) is interested in research focusing on: 

  • Understanding the relationship between Short-Lived Plasma Cells (SLPC)and Long-Lived Plasma Cells (LLPC) and how LLPC mediates autoantibody production in pre-clinical autoimmunity and autoimmune disease
  • Study the sex influences in vaccine research utilizing the new approach methodologies (NAMs) and computational modeling of plasma cells in human health and disease.
  • Accelerating scientific discovery in diagnosis, treatment, prevention, and cures and enhancing health for people with autoimmune disease.

This office does not award grants. Applications must be relevant to the objectives of at least one of the participating NIH Institutes and Centers listed in this topic. 

ICO Scientific Contact:
Victoria Shanmugam, MBBS, MRCP, FACR, CCD
[email protected]

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