# Decay Accelerating Factor and B cell Immunity

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $423,750

## Abstract

Project Summary
Humoral immunity crucially protects against pathogens but can function as a pathogenic mediator of multiple
autoimmune and alloimmune disease processes, the latter including chronic graft vs. host disease and
antibody-mediated solid organ transplant rejection. Development of antigen-specific antibody responses
requires T cell-dependent B cell activation and the formation of germinal centers (GC), transient lymphoid
structures where somatic hypermutation and affinity maturation events result in the generation of high affinity,
antibody-producing plasma cells (PC) and memory B cells (Bmem). The physiological signals that control GC
formation and GC B cell fates are incompletely characterized. Our preliminary data identify a previously
unappreciated role for decay accelerating factor (DAF or CD55), a cell surface-expressed complement
regulatory protein, in controlling GC reactions and their resultant output, the production of PC and Bmem. Our
data support the hypothesis that optimal GC function requires downregulation of cell surface expressed DAF
on responding B cells, a process that lifts restraint on local, alternative pathway complement activation and
facilitates C3- and C5-convertase formation and production of C3 and C5 cleavage products. This process
promotes C3a/C3aR1 and C5a/C5aR1 ligations on GC B cells, which would in turn transduce signals
controlling GC B cell proliferation, survival, somatic hypermutation, and/or affinity maturation, and as a
consequence, influence differentiation into memory B cells and/or plasma cells. We will test this paradigm-
shifting hypothesis using unique biological reagents and through 3 interactive aims: 1) To determine the effects
of B cell-expressed DAF, C3aR1 and C5aR1 on T cell-dependent humoral immune responses and distinguish
them from the effects of B cell-expressed CD21. 2) To determine the cellular and molecular mechanisms
through which DAF downregulation and enhanced signaling through C3aR1/C5aR1 in B cells drive affinity
maturation. 3) To determine the molecular basis of DAF downregulation on B cells. This comprehensive
analysis performed by a multi-PI team with expertise in complement biology (Heeger) and B cell biology
(Dominguez-Sola) is likely to provide new insight into fundamental mechanisms of GC dynamics and function.
The results have the potential to guide second order studies aimed at exploiting the complement/B cell axis to
either inhibit development of pathogenic B cell responses (e.g. in transplantation or autoimmunity) or augment
B cell response (e.g. in response to vaccines).

## Key facts

- **NIH application ID:** 9956985
- **Project number:** 5R01AI141434-02
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** David Dominguez-Sola
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2019-06-17 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9956985

## Citation

> US National Institutes of Health, RePORTER application 9956985, Decay Accelerating Factor and B cell Immunity (5R01AI141434-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9956985. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*