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

作者:Fairfax Kirsten A; Corcoran Lynn M; Pridans Clare; Huntington Nicholas D; Kallies Axel; Nutt Stephen L; Tarlinton David M*
来源:The Journal of Immunology, 2007, 178(7): 4104-4111.
DOI:10.4049/jimmunol.178.7.4104

摘要

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-1(GFP/+)), 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 Ill 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-1(GFP/+) B1 and B2 cells both gave rise to ASCs in the bone marrow, suggesting no intrinsic barriers to BI cell entry into the long-lived ASC compartment.