Long-term proliferating early pre B cell lines and clones with the potential to develop to surface Ig-positive, mitogen reactive B cells in vitro and in vivo.
Cell lines and clones were established from PB76-positive mouse fetal liver at day 13 and 14 of gestation, which proliferated with division times of a day in serum-substituted cultures under the stimulatory influence of adherent stromal cells and the cytokine IL-7 for periods longer than half a year. These lines expressed varying levels of the B lymphocyte lineage related markers PB76, B220, BP-1, VpreB and lambda 5, but no surface Ig or MHC class II molecules. All clones expressed PB76, VpreB and lambda 5 in a high percentage of cells, while B220 and/or BP-1 expression was low or undetectable in some. A cell line, and several clones established from it, all had kappa and lambda light chain genes in germ-line configuration. Either one or both of their H-chain-gene containing chromosomes carried a DH to JH. These pre B cell lines and clones could be induced to VH to DH and VL to JL rearrangements. This resulted in the development of varying percentages of sIg-positive surface, MHC class II negative, LPS-reactive B cells within 2-3 days, in the absence of contacts with stromal cells and/or IL-7. When injected into SCID mice, the cultured pre B cells populated the spleen of these mice to 5% with surface Ig-, MHC class II-positive LPS-reactive cells for greater than 25 weeks. The long-term in vitro proliferative capacity of these DH-JH rearranged pre B cell clones makes them major candidates for committed stem cells of the B lineage.
Rolink
A
A
Basel Institute for Immunology, Switzerland.
Kudo
A
A
Karasuyama
H
H
Kikuchi
Y
Y
Melchers
F
F
D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells; D005260:Female; D005333:Fetus; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D015851:Interleukin-7 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D051381:Rats; D011917:Rats, Inbred Lew; D011947:Receptors, Antigen, B-Cell / Q000032:analysis*; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000276:immunology
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II; D015851:Interleukin-7; D007378:Interleukins; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins