# Characterization of B Lymphocyte Deficiency in Pediatric Sickle Cell Disease

> **NIH NIH K23** · BAYLOR COLLEGE OF MEDICINE · 2024 · $163,172

## Abstract

PROJECT SUMMARY
Infections are frequent complications in sickle cell disease (SCD), occurring in up to 45% of patients. In Africa,
where up to 90% of children with SCD die by age 5 years, many of these deaths are attributed to infection. In
SCD, the spleen is damaged in infancy and results in marginal zone B cell deficiency. The clinical implications
of B cell deficiency in SCD are not fully understood and requires investigating both disease-intrinsic and -
extrinsic modifiers of B cell subsets. In this investigation, I will quantify B cell subsets in children with and
without SCD in Texas and in Tanzania, investigate mechanisms of B cell deficiency, and compare them to
important clinical endpoints.
Aim 1: Characterize mechanisms of MZB deficiency in SCD. Hypotheses: There is a difference in the
development, survival, and function of B cells from SCD and non-SCD subjects due to B-cell intrinsic factors.
Differences in B cell populations may be due to differences in kinetics of differentiation and proliferation and/or
survival. To examine differentiation and proliferation, I will measure the efficiency of differentiation of
transitional B cells from SCD and non-SCD donors into MZBs, and MZBs into plasma cells using an in vitro B
cell co-culture system. To examine survival, I will measure the rate of apoptosis and expression of markers of
apoptosis (e.g. annexin V, caspase 3/9, BCL2) in native and culture-derived MZBs in culture.
Aim 2: Determine the effect of the microenvironment of the spleen in SCD on B cells. Hypothesis:
Extrinsic factors such as the inflammatory environment in SCD impair B cell development, survival, and
function. To examine the effect of the microenvironment on B cells in culture, I will culture non-SCD B cells in
media supplemented with SCD serum or spleen extract. To investigate which components of the extract impact
B cells, I will develop a cytokine profile for the extract and serum using multiplex ELISA.
Aim 3: Determine whether low MZB is associated with infectious and inflammatory complications of
SCD. Hypothesis: Life-threatening infections in SCD are more common among children with severe MZB
deficiency. To determine whether B-cell tropic viruses have a confounding effect on MZB number, I will
measure immune response to EBV and malaria using a custom multiplex ELISA panel. To determine whether
infectious complications are associated with more severe MZB deficiency in SCD, I will compare MZB among
children with and without complications such as acute chest, osteomyelitis, or bacteremia.
Despite a shared driver mutation, the clinical phenotype in SCD is highly variable. Together, the studies in this
proposal will overcome critical barriers to risk-stratifying patients for infectious and inflammatory complications
of SCD. Increased insights into how SCD catalyzes B cell deficiency may help identify novel therapeutic
targets or biomarkers to mitigate the impact of infections on SCD. My central hypothesis is that B cell
a...

## Key facts

- **NIH application ID:** 10854886
- **Project number:** 5K23HL148548-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Venee N Tubman
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $163,172
- **Award type:** 5
- **Project period:** 2020-06-20 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10854886

## Citation

> US National Institutes of Health, RePORTER application 10854886, Characterization of B Lymphocyte Deficiency in Pediatric Sickle Cell Disease (5K23HL148548-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10854886. Licensed CC0.

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