# Unearthing phagocytic IgM+ plasma cells and their previously unrecognized roles in innate and adaptive immunity

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2020 · $201,250

## Abstract

Project summary: Antibodies are the crown jewel of humoral adaptive immune responses and, plasma cells (PCs)
are by far the most specialized and main antibody-secreting cells. PCs differentiate from B lymphocytes following
microbial- or CD4 T cell-induced differentiation. Depending on the B cells from which they derive, PCs will largely
secrete IgM, IgG or IgA. Until very recently, PCs were viewed exclusively as antibody-producing factories. Here we
show for the first time that a large subset of splenic PCs bearing surface IgM (IgM+ PCs) have a strikingly high
phagocytic capacity. In contrast, all class-switched PCs (i.e., IgG+ PCs) lack this capacity. Thus, our discovery
that plasma cells, a central component of adaptive immunity, play a critical innate immune role, is
potentially transformative. The overarching goal of this proposal is therefore to explore the consequences of this
previously unrecognized phagocytic capacity of IgM+ PCs both in innate and adaptive immunity. Phagocytosis has
evolved from playing a key function in innate immunity and tissue remodeling to having a pivotal role at the
crossroads between innate and adaptive immunity. This ancient function is traditionally thought to be performed by
professional phagocytes, including polymorphonuclear cells (PMNs), monocytes and macrophages and peritoneal
cavity B-1 B cells. Our preliminary data, indicates the existence of a new phagocyte type, phagocytic plasma cells
(PhPCs), which have the potential to play novel roles in immunity. Thus far, our preliminary studies have shown that
PhPCs in vitro and in vivo phagocytose a variety of targets, including latex beads and E. coli. Critically, upon
lipopolysaccharide (LPS) treatment of mice, we observe a ~16 fold increase in splenic PhPCs numbers, which
represents ~1% of total splenocytes. Moreover, PhPCs express surface CD86 and MHC II and, 3D confocal
imaging have revealed that many PCs are in close proximity to CD4 T cells, thus suggesting a biological
significance in their potential capacity to present antigen. Our new findings have lead us to hypothesize previously
unrecognized antibody-independent roles of splenic PhPCs in innate and adaptive immunity, including: 1- Their
control and clearing of microbes; 2- Their modulation of immunity through cytokine and chemokine secretion; 3-
Their capacity to present phagocytosed antigens to T cells and thus, initiate adaptive immune responses. To test
these hypotheses, we will be using mice conditionally lacking Blimp-1 in the B-cell compartment (Blimp-1-cKO
mice). Critically, these Blimp-1-cKO mice lack PCs, thus making it possible to compare potential differences
between mice with and without splenic PCs. The specific aims of this proposal are: AIM 1. To investigate key roles
of PhPCs in phagocytosis-elicited innate immune mechanisms; AIM 2. To characterize the mechanisms by which
PhPCs bridge innate with adaptive immunity. Our discovery of PhPCs represents a paradigm shift in our
understand...

## Key facts

- **NIH application ID:** 9829530
- **Project number:** 5R21AI138078-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** J. ORIOL SUNYER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,250
- **Award type:** 5
- **Project period:** 2018-12-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829530

## Citation

> US National Institutes of Health, RePORTER application 9829530, Unearthing phagocytic IgM+ plasma cells and their previously unrecognized roles in innate and adaptive immunity (5R21AI138078-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9829530. Licensed CC0.

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