# Determining Enhanced Inflammatory B cell Function in African Americans with MS

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $254,250

## Abstract

Why African American and Latin Americans present with greater multiple sclerosis (MS) disease
severity has not been investigated beyond retrospective clinical chart review, and risk
association studies. B cells inform MS diagnostic, severity and prognostic assessments through
their immunobiological activity. Thanks to the dramatic efficacy of B cell depletion therapy, we
now know that B cells are principal drivers of MS clinical activity. We propose that B cell-based,
ancestry-dependent functional difference in MS holds clinically valuable mechanistic insight.
Such insight would be supportive of an emergent pattern where ancestry-mediated
immunobiological differences underlie ancestry-disparate clinical severity, heterogeneity and
prevalence.
In this study, we test our hypothesis that MS patients of African ancestry possess greater T-
dependent inflammatory B cell function relative to those of Caucasian ancestry. Our
preliminary findings support this hypothesis. At steady-state ex vivo (directly from subject
peripheral blood) circulating antibody secreting cell (ASC) subset frequencies are increased in
BA/LAwMS relative to CAwMS. Further, isolated B cells more readily differentiate into ASCs
compared to CAwMS upon in vitro T-dependent stimulation. These differences are absent
amongst healthy donors. Our preliminary findings imply that underlying ancestry-mediated
differences drive B cell differentiation toward ASC fate. We will specify mechanisms associated
with these findings, ultimately applying fine-resolution SNP-based ancestral analysis to ex vivo
and in vitro assay readouts. Specifically, we will conduct longitudinal ex vivo assessment of
ASC as well as antigen presenting function-associated proteins on memory B cells. We will also
delineate in vitro T-dependent and T-independent ASC differentiation, expression of class-
switched memory B cell inflammatory products and enhanced STAT3 signaling amongst this
population.
This project (1) directly investigates inflammatory B-cell function comparing BA/LAwMS and
CAwMS for the first time, and (2) builds upon a nascent paradigm (to our knowledge) initially
demonstrated in limited fashion within systemic lupus erythematosus. Our project thus fits key
criteria of the R21 mechanism by nuancing the emergent idea of B cell-driven ancestry-
dependent disease disparity. As for impacting clinical research, our project is in-line with current
and future precision medicine initiatives geared towards identifying and responding to biological
variation across formerly subsumed or otherwise underrepresented ethnic groups.

## Key facts

- **NIH application ID:** 9896484
- **Project number:** 1R21AI144819-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** TIMOTHY VARTANIAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $254,250
- **Award type:** 1
- **Project period:** 2020-02-03 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896484

## Citation

> US National Institutes of Health, RePORTER application 9896484, Determining Enhanced Inflammatory B cell Function in African Americans with MS (1R21AI144819-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9896484. Licensed CC0.

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