# Delineating The Differences Between Short-Lived And Long-Lived Plasma Cells

> **NIH NIH R21** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $254,250

## Abstract

Abstract
 Secreted antibodies by plasma cells provide antigen specific humoral immunity, with long-lived plasma
cells playing a critical role in immune memory responses. While recent studies have provided considerable
insight into terminal differentiation of B cells into plasma cells, exactly how plasma cells are maintained long
after antigen exposure remains enigmatic. Conditional gene targeting in animal models has permitted
delineation of gene function and signaling networks in a cell type specific manner. Until now this technique
could not be efficiently applied to plasma cells because of the lack of plasma cell specific Cre alleles. We
propose to generate two strains which will allow genetic manipulation of this poorly understood lineage. Using
state-of-the-art CRISPR/Cas9 gene editing approach we have knocked-in a codon optimized Cre into the IgJ
locus that encodes the J chain polypeptide expressed selectively in all plasma cells. J chain polypeptide is
necessary for multimerization of secreted IgM and IgA, but is expressed in all murine plasma cells. We will also
generate a second Cre model, in which a codon optimized ligand inducible iCreERt2 will be knocked-into the
same IgJ locus. Preliminary analysis of our first IgJ-iCre mice is highly promising, revealing plasma-cell specific
expression of Cre recombinase. We will perform detailed analysis to further validate the cell specificity and
efficiency of Cre activity by crossing the IgJ-iCre and IgJ-iCreERt2 mice to a reporter strain.
 The two plasma cell specific Cre alleles will, for the first time, provide the means to perform conditional
gene targeting in this poorly understood lineage. Plasma cells play a central role in immune responses to
pathogens and immunizations and are critical players in autoimmunity and cancer. These two plasma cell
specific Cre lines have potential to facilitate a wide range of studies into signaling networks required for plasma
cell differentiation, survival and function, multiple myeloma pathogenesis as well as genetic studies looking into
the exact contribution of plasma cells to autoimmune and inflammatory diseases. The priority for our
immunology lab, as outlined in Aim 2, is to investigate the role of B cell receptor (BCR) signaling and affinity of
the BCR for antigen in the maintenance of long-lived plasma cells. We also intend to use the lineage tracing
approach that will be made possible by the IgJ-iCreERt2 mice to characterize the differences between plasma
cells that develop shortly after the immunogenic challenge and long-lived plasma cells that can be found in the
bone marrow months after antigen exposure.

## Key facts

- **NIH application ID:** 9822951
- **Project number:** 5R21AI137752-02
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Sergei Borisovich Koralov
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $254,250
- **Award type:** 5
- **Project period:** 2018-11-15 → 2020-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9822951

## Citation

> US National Institutes of Health, RePORTER application 9822951, Delineating The Differences Between Short-Lived And Long-Lived Plasma Cells (5R21AI137752-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9822951. Licensed CC0.

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