An interleukin-6 transgene expressed in B lymphocyte lineage cells overcomes the T cell-dependent establishment of normal levels of switched immunoglobulin isotypes.
Long-term proliferating, stromal cell/interleukin (IL)-7-reactive precursor B cell lines established from fetal liver and bone marrow of human IL-6-transgenic B6Ld46 mice produce and secrete human IL-6. When transplanted into severe-combined immunodeficient (SCID) or Rag2 knockout (Rag2-T) mice, these pre-B-cell lines establish a part of the B cell compartment but yield no T cells, as do pre-B cell lines from genetically matched non-transgenic mice. Within 2 to 3 months after transplantation, the serum of mice transplanted with pre-B cells from normal mice contains normal levels of IgM (200-600 micrograms/ml) but 10-100-fold lower levels of the IgG subclasses and of IgA. In contrast, the sera of mice transplanted with IL-6 transgenic pre-B cells contain not only IgM, but also IgG and IgA at nearly normal levels. The results indicate that at least a part of the plasmacytosis and elevated IgG production observed previously in the IL-6-transgenic mice appears to be due to a T cell-independent activation of IgG and IgA production by the IL-6-secreting pre-B cells and their differentiated progeny in the immunodeficient hosts.
Oka
Y
Y
Basel Institute for Immunology, Switzerland.
Rolink
A G
AG
Suematsu
S
S
Kishimoto
T
T
Melchers
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D001853:Bone Marrow / Q000196:embryology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000196:embryology / Q000276:immunology; D008211:Lymphocyte Cooperation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; D011994:Recombinant Proteins; C064655:V(D)J recombination activating protein 2