Transcriptome analysis in primary B lymphoid precursors following induction of the pre-B cell receptor.
Pre-BCR signals are part of a checkpoint where early precursor (pre-) B cells with a pairing Ig muH chain (muHC) are clonally expanded before they differentiate into IgL-rearranging, resting pre-B cells. A pre-BCR consists of two muHCs, two surrogate L chains and the signal transducer Igalpha/Igbeta. The molecular circuits by which the pre-BCR controls proliferation and differentiation of pre-B cells are poorly characterized. Therefore, we identified the differential transcriptome by genome-wide expression profiling in progenitor (pro-) B cells from a Rag2-deficient mouse, in which the expression of a transgenic muHC and thus a pre-BCR as well as pre-BCR-mediated clonal expansion can be controlled by tetracycline (muHC-inducible mouse). This analysis revealed that pre-BCR signals upregulate components of the BCR signalosome, open the IgL chain (LC) locus and induce the krüppel-like transcription factor KLF2, a key regulator of quiescence and lymphocyte migration. Hence, pre-BCR signals establish the molecular network for BCR signaling even before the production of an IgLC and induce the expression of KLF2, a candidate for controlling clonal expansion and migration of functional pre-B cells.
Division of Molecular Immunology, Department of Internal Medicine III, Nikolaus-Fiebiger-Center, University of Erlangen-Nürnberg, Glückstrasse 6, D-91054 Erlangen, Germany.
Wolfgang
W
Schuh
Silke
S
Meister
Kai
K
Herrmann
Harald
H
Bradl
Hans-Martin
HM
Jäck
D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054420:Pre-B Cell Receptors / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D013752:Tetracycline / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D018941:Antigens, CD19; C014609:IgK; D007148:Immunoglobulin mu-Chains; D007136:Immunoglobulins; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D054420:Pre-B Cell Receptors; D013752:Tetracycline