Different kinetics of blimp-1 induction in B cell subsets revealed by reporter gene.
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 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-1(GFP/+) 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.
Fairfax
Kirsten A
KA
Immunology Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, Australia.
Corcoran
Lynn M
LM
Pridans
Clare
C
Huntington
Nicholas D
ND
Kallies
Axel
A
Nutt
Stephen L
SL
Tarlinton
David M
DM
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017930:Genes, Reporter / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D007136:Immunoglobulins / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051560:Proto-Oncogene Proteins c-bcl-6; D050436:Regulatory Elements, Transcriptional; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
C490010:Bcl6 protein, mouse; D004268:DNA-Binding Proteins; D007136:Immunoglobulins; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; C513258:Prdm1 protein, mouse; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D000074462:Positive Regulatory Domain I-Binding Factor 1