Normal B-1a cell development requires B cell-intrinsic NFATc1 activity.
B-1a cells, an anatomically, phenotypically, and functionally distinct subset of B cells that produce the bulk of natural serum IgM and much of gut-associated IgA, are an important component of the early response to pathogens. Because the induced expression of CD5, a hallmark of B-1a cells, requires a nuclear factor of activated T cells (NFAT)-dependent enhancer, we examined the role of NFAT transcription factors in B-1a development. Here we show that the B-1a compartment is normal in mice lacking NFATc2 but essentially absent in mice lacking NFATc1. Loss of NFATc1 affects both peritoneal and splenic B-1a cells. Because there is a loss of B-1 cells defined by markers other than CD5, NFATc1 is not required simply for CD5 expression on B-1a cells. Using mixed-allotype chimeras and retroviral-mediated gene transduction we show that the requirement for NFATc1 is B cell-intrinsic. We also demonstrate that NFATc1 protein expression is elevated approximately 5-fold in B-1a cells compared with B-2 cells. This is the first definitive demonstration of a B cell-intrinsic function for an NFAT family transcription factor.
Department of Pathology and Graduate Program in Immunology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA. robert.berland@tufts.edu
Robert
R
Berland
Henry H
HH
Wortis
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000473:pathology*; D015153:Blotting, Western; D018956:CD5 Antigens / Q000096:biosynthesis; D002469:Cell Separation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D015151:Immunoblotting; D007070:Immunoglobulin A / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010641:Phenotype; D012190:Retroviridae / Q000235:genetics; D013154:Spleen / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*
D018956:CD5 Antigens; D004268:DNA-Binding Proteins; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D008164:Luminescent Proteins; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C494007:Nfatc2 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D049452:Green Fluorescent Proteins