Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human heumatoid arthritis or common variable immunodeficiency patients reveals defective receptor editing results in the appearance of anergic B cells in humans

ABSTRACT: B cell tolerance is established using deletion, anergy and receptor editing mediated by secondary recombination but it is unclear why autoreactive B cells choose a tolerance mechanism over another. We identified subgroups of patients with either rheumatoid arthritis or common variable immunodeficiency who presented defects in secondary recombination, which correlated with unusual CD21-/lo naïve B cells in their blood. CD21-/lo B cells were unable to induce calcium flux, get activated or proliferate in response to B cell receptor and/or CD40 triggering, suggesting that these B cells are anergic. Moreover, CD21-/lo B cells are often autoreactive and may express anti-nuclear antibodies. Thus, anergy can be a default tolerance mechanism mainly induced when receptor editing fails to silence developing autoreactive B cells. Experiment Overall Design: RNA was extracted from batch sorted CD19+CD21+CD10-CD27- and CD19+CD21-CD10-CD27- naïve B cells isolated from donors using the Absolutely RNA microprep kit (Stratagene). 100-200 ng of RNA was obtained per sample, and the quality of the purified RNA was assessed by the Bioanalyzer from Agilent. Using the Ovation biotin system kit from Nugen, 30-50ng of RNA was amplified and labeled to produce cDNA. Labeled cDNA was hybridized on chips containing the whole human genome (Human Genome U133 2.0 from Affymetrix). Data from CD21+ and CD21- B cell populations were compared in order to determine the gene signature of the newly described CD21- B cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Isabelle Isnardi

PROVIDER: E-GEOD-13917 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Transcription profiling of human heumatoid arthritis or common variable immunodeficiency patients reveals defective receptor editing results in the appearance of anergic B cells in humans

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