Origins of peripheral B cells in IL-7 receptor-deficient mice.
The interleukin 7 (IL-7) signaling pathway is critical for early lymphoid differentiation. We found dramatic perturbations in fetal liver B cell development and confirmed a complete absence of developing B cells in the adult bone marrow in mice lacking the IL-7 receptor alpha (IL-7Ralpha) gene. We show that peripheral B-2 and B-1 cell populations are deficient in IL-7Ralpha-/- mice. B-2 follicular cell and peritoneal B-1 cell percentages are reduced, while B-2 marginal zone cell percentages are increased. A comparison of bone marrow and splenic populations at different ages revealed that the splenic B cell populations seen in adult IL-7Ralpha-/- mice first appear during neonatal development. We have measured N-nucleotide addition at the joints of V(D)J rearrangements in splenic B cells and have used it as a somatic marker to define and separate bone marrow-derived B cells from fetal liver-derived B cells. B cells isolated from the bone marrow and spleen of adult and neonatal IL-7Ralpha-deficient mice harbor high levels of N-nucleotide additions similar to those found in equivalent wild-type B cell populations. We conclude that the majority of splenic B cells in IL-7Ralpha-deficient mice originate from the bone marrow and not the fetal liver.
Hesslein
David G T
DG
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519, USA.
Yang
Shu Yuan
SY
Schatz
David G
DG
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000166:cytology*; D001853:Bone Marrow / Q000196:embryology / Q000254:growth & development; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D015322:Gene Rearrangement, B-Lymphocyte; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020395:Receptors, Interleukin-7 / Q000172:deficiency* / Q000235:genetics; D016415:Sequence Alignment; D013154:Spleen / Q000166:cytology*; D050441:VDJ Exons
D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D004253:DNA Nucleotidylexotransferase