Perspectives on fetal derived CD5+ B1 B cells.
CD5(+) B-cell origins and their predisposition to lymphoma are long-standing issues. Transfer of fetal and adult liver BM Pro-B cells generates B cells with distinct phenotypes: fetal cells generate IgM(high) IgD(low) CD5(+) , whereas adult cells IgM(low) IgD(high) CD5(-) . This suggests a developmental switch in B lymphopoiesis, similar to the switch in erythropoiesis. Comparison of mRNA and miRNA expression in fetal and adult Pro-B cells revealed differential expression of Lin28b mRNA and Let-7 miRNA, providing evidence that this regulatory axis functions in the switch. Recent work has shown that Arid3a is a key transcription factor mediating fetal-type B-cell development. Lin28b-promoted fetal development generates CD5(+) B cells as a consequence of positively selected self-reactivity. CD5(+) B cells play important roles in clearance of apoptotic cells and in protective immune responses, but also pose a risk of progression to leukemia/lymphoma. Differential Lin28b expression in fetal and adult human B-cell precursors showed that human B-cell development may resemble mouse, with self-reactive "innate-like" B cells generated early in life. It remains to be determined whether such human B cells have a higher propensity to leukemic progression. This review describes our recent research with CD5(+) B cells and presents our perspective on their role in disease.
Fox Chase Cancer Center, Philadelphia, PA, USA.
Richard R
RR
Hardy
Fox Chase Cancer Center, Philadelphia, PA, USA.
Kyoko
K
Hayakawa
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology*; D005333:Fetus; D006801:Humans; D015448:Leukemia, B-Cell / Q000276:immunology; D038041:Lymphopoiesis / Q000276:immunology*; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology*
D018956:CD5 Antigens
B-cell development; B-cell leukemia; B1a cells; CD5+ B cells; Stem cells; Transgenic mouse models