Retinoids accelerate B lineage lymphoid differentiation.
Retinoids are known to have potent effects on hemopoietic stem cell integrity, and our objective was to learn whether they influence cells destined to replenish the immune system. Total CD19+ B lineage cells increased substantially in the marrow and spleens of all-trans retinoic acid (ATRA)-treated C57BL6 mice, while lymphoid progenitors were reduced. All B lymphoid progenitors were targets of ATRA in culture and overall cell yields declined without reductions in proliferation. Remarkably, ATRA shortened the time required for primitive progenitors to generate CD19+ cells. PCR analysis and a panel of retinoid acid receptor (RAR)/retinoid X receptor agonist treatments suggested that RARalpha mediates these responses. The transcription factors EBF1 and Pax-5 were elevated during treatment and ATRA had similar effects on human B cell differentiation. That is, it inhibited the expansion of human progenitor cells and accelerated their differentiation to B lineage cells. There may be previously unsuspected side effects of ATRA therapy, and the new findings suggest retinoids can normally contribute to the lymphopoietic environment in bone marrow.
Chen
Xinrong
X
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Esplin
Brandt L
BL
Garrett
Karla P
KP
Welner
Robert S
RS
Webb
Carol F
CF
Kincade
Paul W
PW
D000818:Animals; D018941:Antigens, CD19 / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018655:Lymphocyte Count; D038041:Lymphopoiesis; D051379:Mice; D008810:Mice, Inbred C57BL; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D054448:Precursor Cells, B-Lymphoid / Q000187:drug effects*; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism; D012176:Retinoids / Q000494:pharmacology / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology* / Q000502:physiology
D018941:Antigens, CD19; D004268:DNA-Binding Proteins; C489921:Ebf1 protein, mouse; D051757:PAX5 Transcription Factor; C497282:Pax5 protein, mouse; D047488:Retinoid X Receptors; D012176:Retinoids; D015534:Trans-Activators; D014212:Tretinoin