A thymic stromal cell line supports in vitro development of surface IgM+ B cells and produces a novel growth factor affecting B and T lineage cells.
A thymic stromal cell line with a medullary phenotype (Z210R.1) supported the differentiation of surface IgM+ B cells when cocultured with fetal liver cells in vitro. Conditioned medium (CM) from this cell line supported the long-term growth of a B cell line (NAG8/7) isolated from cocultures and enhanced the proliferation of unfractionated thymocytes to suboptimal concentrations of anti-CD3 antibodies in vitro. Biological assays of the CM detected interleukin-7 (IL-7) but not IL-1, IL-2, IL-3, IL-4, IL-6, Steel factor (SCF), leukemia inhibitory factor (LIF), or macrophage or granulocyte colony-stimulating factors (M-CSF or G-CSF). The failure of recombinant IL-7 to maintain the long-term growth of NAG8/7 cells and the inability of anti-IL-7 antibodies to significantly affect the response of either NAG8/7 cells or thymocytes to CM suggested the presence of one or more other cytokines in the CM. Analysis of concentrated CM fractionated by anion exchange chromatography revealed a single peak of activity in the NAG8/7 assay with an elution profile that was distinct from IL-7. Two peaks of activity were detected in the thymocyte response to anti-CD3 antibodies; one corresponded to IL-7 and the other corresponded to the same fractions that stimulated NAG8/7 cells. The second peak of thymocyte stimulatory activity could not be inhibited by neutralizing anti-IL-7 antibodies. In addition to producing a cytokine with unique properties, this thymic stromal cell exhibits a functional homology to bone marrow or fetal liver stromal cells not previously appreciated.
Friend
S L
SL
Department of Immunology, University of Washington, Seattle 98195.
Hosier
S
S
Nelson
A
A
Foxworthe
D
D
Williams
D E
DE
Farr
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000032:analysis; D002450:Cell Communication; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D002852:Chromatography, Ion Exchange; D017077:Culture Media, Conditioned / Q000032:analysis / Q000494:pharmacology; D005434:Flow Cytometry; D006133:Growth Substances / Q000378:metabolism* / Q000502:physiology*; D006410:Hematopoiesis / Q000502:physiology; D007075:Immunoglobulin M / Q000032:analysis*; D015851:Interleukin-7 / Q000032:analysis / Q000276:immunology; D008099:Liver / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000032:analysis*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology* / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D017077:Culture Media, Conditioned; D006133:Growth Substances; D007075:Immunoglobulin M; D015851:Interleukin-7; D011947:Receptors, Antigen, B-Cell