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Discriminating gene expression profiles of memory B cell subpopulations.

ABSTRACT: Morphologically and functionally distinct subpopulations of human memory B (B(Mem)) cells are identifiable by either their expression of CD27 or Fc receptor-like 4 (FCRL4), an immunoglobulin domain containing a receptor with strong inhibitory potential. We have conducted comparative transcriptome and proteome analyses of FCRL4(+) and FCRL4(-) B(Mem) cells and found that these two subsets have very distinctive expression profiles for genes encoding transcription factors, cell-surface proteins, intracellular signaling molecules, and modifiers of the cell-cycle status. Among the differentially expressed transcription factors, runt-related transcription factor 1 (RUNX1) transcript levels were up-regulated in FCRL4(-) cells, whereas RUNX2 transcripts were preferentially detected in FCRL4(+) cells. In vitro evidence for FCRL4 promoter responsiveness and in vivo promoter occupancy suggested that RUNX transcription factors are involved in the generation of these B(Mem) cell subpopulations. A distinctive signature profile was defined for the FCRL4(+) B(Mem) cells by their expression of CD11c, receptor activator for nuclear factor kappaB ligand, and FAS cell-surface proteins, in combination with increased levels of SOX5, RUNX2, DLL1, and AICDA expression. We conclude that this recently identified subpopulation of B(Mem) cells, which normally resides in epithelial tissue-based niches, may serve a unique role in mucosal defense and, conversely, as a target for neoplastic transformation events.

SUBMITTER: Ehrhardt GR

PROVIDER: S-EPMC2525601 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Discriminating gene expression profiles of memory B cell subpopulations.

Ehrhardt Götz R A GR Hijikata Atsushi A Kitamura Hiroshi H Ohara Osamu O Wang Ji-Yang JY Cooper Max D MD

The Journal of experimental medicine 20080714 8

Morphologically and functionally distinct subpopulations of human memory B (B(Mem)) cells are identifiable by either their expression of CD27 or Fc receptor-like 4 (FCRL4), an immunoglobulin domain containing a receptor with strong inhibitory potential. We have conducted comparative transcriptome and proteome analyses of FCRL4(+) and FCRL4(-) B(Mem) cells and found that these two subsets have very distinctive expression profiles for genes encoding transcription factors, cell-surface proteins, in ...[more]

PMID: 18625746

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Project description:ObjectiveDepression has been associated with metabolomic alterations. Depressive and anxiety disorders are often comorbid diagnoses and are suggested to share etiology. We investigated whether differential metabolomic alterations are present between anxiety and depressive disorders and which clinical characteristics of these disorders are related to metabolomic alterations.MethodsData were from the Netherlands Study of Depression and Anxiety (NESDA), including individuals with current comorbid anxiety and depressive disorders (N = 531), only a current depression (N = 304), only a current anxiety disorder (N = 548), remitted depressive and/or anxiety disorders (N = 897), and healthy controls (N = 634). Forty metabolites from a proton nuclear magnetic resonance lipid-based metabolomics panel were analyzed. First, we examined differences in metabolites between disorder groups and healthy controls. Next, we assessed whether depression or anxiety clinical characteristics (severity and symptom duration) were associated with metabolites.ResultsAs compared to healthy controls, seven metabolomic alterations were found in the group with only depression, reflecting an inflammatory (glycoprotein acetyls; Cohen's d = 0.12, p = 0.002) and atherogenic-lipoprotein-related (e.g., apolipoprotein B: Cohen's d = 0.08, p = 0.03, and VLDL cholesterol: Cohen's d = 0.08, p = 0.04) profile. The comorbid group showed an attenuated but similar pattern of deviations. No metabolomic alterations were found in the group with only anxiety disorders. The majority of metabolites associated with depression diagnosis were also associated with depression severity; no associations were found with anxiety severity or disease duration.ConclusionWhile substantial clinical overlap exists between depressive and anxiety disorders, this study suggests that altered inflammatory and atherogenic-lipoprotein-related metabolomic profiles are uniquely associated with depression rather than anxiety disorders.

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Discriminating gene expression profiles of memory B cell subpopulations.

Publications

Discriminating gene expression profiles of memory B cell subpopulations.

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