Different kinetics of Blimp-1 induction in B cell subsets revealed by reporter gene

Kirsten A. Fairfax, Lynn M. Corcoran, Clare Pridans, Nicholas D. Huntington, Axel Kallies, Stephen L. Nutt, David M. Tarlinton

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Abstract

The transcriptional repressor Blimp-1 (B lymphocyte-induced maturation protein 1) has been described as a "master regulator" of B cell differentiation into Ab-secreting cells (ASCs). Although there is mounting evidence for the importance and necessity of Blimp-1 in plasma cell development, there is uncertainty as to the role it plays in B cell differentiation of B cell subsets and the way in which it may interact with other transcription factors such as Pax5 and BcI6 during ASC differentiation. Using a mouse expressing GFP under the control of the Blimp-1 regulatory elements (Blimp-1GFP/+), we examined the kinetics of Blimp-1 up-regulation in purified B cell subsets following activation. Bl cells showed the most rapid and pronounced up-regulation of Blimp-1 in response to the mitogens tested, followed by marginal zone B cells and then conventional B2 cells. Interestingly, only Bl cells substantially up-regulated Blimp-1 expression in response to CpG. Bl cells secreted negligible Ig upon isolation but were able to up-regiilate Blimp-1 and initiate Ig secretion within 28 Ii of stimulation. Also of interest, B1 cells have a transcriptional factor profile that is intermediate between a naive B cell and an ASC, indicative of the semiactivated state of B1 cells. Transferred naive Blimp-1GFP/+ B1 and B2 cells both gave rise to ASCs in the bone marrow, suggesting no intrinsic barriers to B1 cell entry into the long-lived ASC compartment.

Original languageEnglish
Pages (from-to)4104-4111
Number of pages8
JournalJournal of Immunology
Volume178
Issue number7
DOIs
Publication statusPublished - 1 Apr 2007
Externally publishedYes

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