PU.1 is not strictly required for B cell development and its absence induces a B-2 to B-1 cell switch.
In this paper, we describe the unexpected outgrowth of B lineage cells from PU.1(-/-) fetal liver cultures. The cells express all early B cell genes tested, including the putative PU.1 target genes IL-7R and EBF but not B220, and can produce immunoglobulin M. However, we observed a delay in the PU.1(-/-) B cell outgrowth and reduced precursor frequencies, indicating that although PU.1 is not strictly required for B cell commitment, it facilitates B cell development. We also ablated PU.1 in CD19-expressing B lineage cells in vivo, using a Cre-lox approach that allows them to be tracked. PU.1 excision resulted in a shift from B-2 cells to B-1-like cells, which dramatically increased with the age of the mice. Our data indicate that this shift is predominantly caused by a B-2 to B-1 cell reprogramming. Furthermore, we found that B-2 cells express substantially more PU.1 than B-1 cells, which is consistent with the idea that maintenance of the B-2 cell phenotype requires relatively high levels of PU.1, but B-1 cells require little.
Ye
Min
M
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Ermakova
Olga
O
Graf
Thomas
T
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D002478:Cells, Cultured; D015536:Down-Regulation; D015322:Gene Rearrangement, B-Lymphocyte; D007075:Immunoglobulin M / Q000096:biosynthesis; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000172:deficiency / Q000502:physiology*; D000099232:Proto-Oncogene Protein Spi-1
D007075:Immunoglobulin M; D017493:Leukocyte Common Antigens; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1