Racial differences in B cell receptor signaling pathway activation

Diane M. Longo, Brent Louie, Kavita Mathi, Zoltan Pos, Ena Wang, Rachael E. Hawtin, Francesco M. Marincola, Alessandra Cesano

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: Single-cell network profiling (SCNP) is a multi-parametric flow cytometry-based approach that simultaneously measures basal and modulated intracellular signaling activity in multiple cell subpopulations. Previously, SCNP analysis of a broad panel of immune signaling pathways in cell subsets within PBMCs from 60 healthy donors identified a race-associated difference in B cell anti-IgD-induced PI3K pathway activity.Methods: The present study extended this analysis to a broader range of signaling pathway components downstream of the B cell receptor (BCR) in European Americans and African Americans using a subset of donors from the previously analyzed cohort of 60 healthy donors. Seven BCR signaling nodes (a node is defined as a paired modulator and intracellular readout) were measured at multiple time points by SCNP in PBMCs from 10 healthy donors [5 African Americans (36-51 yrs), 5 European Americans (36-56 yrs), all males].Results: Analysis of BCR signaling activity in European American and African American PBMC samples revealed that, compared to the European American donors, B cells from African Americans had lower anti-IgD induced phosphorylation of multiple BCR pathway components, including the membrane proximal proteins Syk and SFK as well as proteins in the PI3K pathway (S6 and Akt), the MAPK pathways (Erk and p38), and the NF-κB pathway (NF-κB). In addition to differences in the magnitude of anti-IgD-induced pathway activation, racial differences in BCR signaling kinetic profiles were observed. Further, the frequency of IgD+ B cells differed by race and strongly correlated with BCR pathway activation. Thus, the race-related difference in BCR pathway activation appears to be attributable at least in part to a race-associated difference in IgD+ B cell frequencies.Conclusions: SCNP analysis enabled the identification of statistically significant race-associated differences in BCR pathway activation within PBMC samples from healthy donors. Understanding race-associated contrasts in immune cell signaling responses may be one critical component for elucidation of differences in immune-mediated disease prevalence and treatment responses.

Original languageEnglish
Article number113
JournalJournal of Translational Medicine
Volume10
Issue number1
DOIs
Publication statusPublished - 6 Jun 2012
Externally publishedYes

Fingerprint

B-Lymphocytes
Chemical activation
Cells
Immunoglobulin D
Tissue Donors
Phosphatidylinositol 3-Kinases
African Americans
Cell signaling
Phosphorylation
Flow cytometry
Modulators
Proteins
Membranes
S 6
Kinetics
Immune System Diseases
anti-IgD
Flow Cytometry
Membrane Proteins

Keywords

  • BCR signaling
  • Multi-parameter flow cytometry
  • Race

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Longo, D. M., Louie, B., Mathi, K., Pos, Z., Wang, E., Hawtin, R. E., ... Cesano, A. (2012). Racial differences in B cell receptor signaling pathway activation. Journal of Translational Medicine, 10(1), [113]. https://doi.org/10.1186/1479-5876-10-113

Racial differences in B cell receptor signaling pathway activation. / Longo, Diane M.; Louie, Brent; Mathi, Kavita; Pos, Zoltan; Wang, Ena; Hawtin, Rachael E.; Marincola, Francesco M.; Cesano, Alessandra.

In: Journal of Translational Medicine, Vol. 10, No. 1, 113, 06.06.2012.

Research output: Contribution to journalArticle

Longo, DM, Louie, B, Mathi, K, Pos, Z, Wang, E, Hawtin, RE, Marincola, FM & Cesano, A 2012, 'Racial differences in B cell receptor signaling pathway activation', Journal of Translational Medicine, vol. 10, no. 1, 113. https://doi.org/10.1186/1479-5876-10-113
Longo, Diane M. ; Louie, Brent ; Mathi, Kavita ; Pos, Zoltan ; Wang, Ena ; Hawtin, Rachael E. ; Marincola, Francesco M. ; Cesano, Alessandra. / Racial differences in B cell receptor signaling pathway activation. In: Journal of Translational Medicine. 2012 ; Vol. 10, No. 1.
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