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* Immunology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia;
Department of Experimental Medicine, University of Melbourne, Parkville, Victoria, Australia; and
University of Western Sydney, Hawkesbury Campus, Richmond, New South Wales, Australia
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 Bcl6 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. B1 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 B1 cells substantially up-regulated Blimp-1 expression in response to CpG. B1 cells secreted negligible Ig upon isolation but were able to up-regulate Blimp-1 and initiate Ig secretion within 28 h 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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the National Health and Medical Research Council of Australia. K.A.F. is the recipient of a Dora Lush Postgraduate Fellowship (National Health and Medical Research Council); N.D.H. is the recipient of a Victorian Cancer Council Fellowship; A.K. is the recipient of a Deutsche Forschungsgemeinschaft Fellowship; S.N. was supported by a Metcalf Fellowship (Walter and Eliza Hall Institute, Australia); and L.M.C. and D.M.T. are Senior Research Fellows of the National Health and Medical Research Council.
2 Address correspondence and reprint requests to Dr. David Tarlinton, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, Australia. E-mail address: tarlinton{at}wehi.edu.au
3 Abbreviations used in this paper: MZ, marginal zone; ASC, Ab-secreting cell; Blimp-1, B lymphocyte-induced maturation protein 1; int, intermediate; IRF-4, IFN-regulatory factor 4; XBP-1, X box-binding protein 1.
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