Racial differences in B cell receptor signaling pathway activation

Journal of Translational Medicine

Alessandra Cesano¹  Francesco M Marincola²  Rachael E Hawtin¹  Ena Wang²  Zoltan Pos⁴  Kavita Mathi³  Brent Louie¹  Diane M Longo¹ 

[1] Nodality, South San Francisco, CA 94080, USA;Infectious Disease and Immunogenetics Section, Department of Transfusion Medicine, Clinical Center, and Center for Human Immunology, National Institutes of Health, Bethesda, MD 20892, USA;MedImmune, Mountain View, CA 94043, USA;Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, H-1089, Hungary

关键词: Race;    BCR signaling;    Multi-parameter flow cytometry;   

Others  :  1205968
DOI  :  10.1186/1479-5876-10-113

 received in 2012-04-14, accepted in 2012-06-06,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Longo et al.; licensee BioMed Central Ltd.

【 图 表 】

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