Support of early B-cell differentiation in mouse fetal liver by stromal cells and interleukin-7.
We compared the development of B-cell progenitors with that of myeloid progenitors in fetal liver cells at various gestational ages. Day 12 to 14 fetal liver cells did not form pre-B-cell colonies. Pre-B-cell colonies were developed from day 15 fetal liver cells. The incidence of colonies increased with increases in gestational age and reached a maximum on days 18 to 19. In contrast, the incidence of myeloid colonies formed in the presence of interleukin-3 (IL-3) and erythropoietin did not change significantly during days 13 to 21 of gestation. After coculturing day 13 fetal liver cells with IL-7-producing stromal cell line ST-2, they could respond to IL-7 and proliferate. Analysis of the phenotypes showed that day 13 fetal liver cells were B220-, IgM-, while culturing day 13 fetal liver cells with ST-2 and untreated day 18 fetal liver cells contained the population of B220+ cells. Even in the presence of IL-7-defective stromal cell line FLS-3, IL-7-responsive cells could be induced from day 13 fetal liver cells. IL-7 acted on B220+ cells and induced pre-B-cell colonies that contained IgM+ cells in the methylcellulose culture. IL-7 mRNA was expressed in days 13 and 18 fetal liver cells but not in pre-B cells or adult liver cells. From these findings, it is suggested that stromal cells or stromal-derived factors but not IL-7 were required for the differentiation from B220- cells to B220+ cells. In the second stage, B220+, IgM- cells proliferated and some of them differentiated to IgM+ cells in the presence of IL-7 alone. The two-step model can apply to in vivo early B lymphopoiesis.
Gunji
Y
Y
Department of Pediatrics, Jichi Medical School, Tochigi-ken, Japan.
Sudo
T
T
Suda
J
J
Yamaguchi
Y
Y
Nakauchi
H
H
Nishikawa
S
S
Yanai
N
N
Obinata
M
M
Yanagisawa
M
M
Miura
Y
Y
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D004921:Erythropoietin / Q000494:pharmacology; D005865:Gestational Age; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007075:Immunoglobulin M / Q000032:analysis; D007377:Interleukin-3 / Q000494:pharmacology; D015851:Interleukin-7 / Q000235:genetics / Q000494:pharmacology*; D017493:Leukocyte Common Antigens; D008099:Liver / Q000166:cytology / Q000196:embryology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis
D000954:Antigens, Surface; D007075:Immunoglobulin M; D007377:Interleukin-3; D015851:Interleukin-7; D012333:RNA, Messenger; D004921:Erythropoietin; D017493:Leukocyte Common Antigens