Regulation of antibody production in vitro by granulocyte-macrophage colony stimulating factor.
The precise molecular characteristics and the mode of action of the T cell derived lymphokines which augment antibody production in vitro remain uncertain. The use of ill-defined culture supernatants to dissect the cellular interactions in vitro involved in antibody production can lead to ambiguous results as the factors may act either on a contaminating non-B-lymphoid population or directly on the B lymphocyte. We report herein the development of a system for measuring in vitro primary antibody responses by murine spleen cells in which endogenous lymphokine production has been minimized by the in vivo administration of cytotoxic antibodies to deplete T lymphocytes and the addition of the glucocorticosteroid, dexamethasone, throughout the culture period. Using such an assay, a lymphokine activity was detected which was capable of augmenting the plaque forming cell response. This lymphokine was present in culture supernatant derived from the lectin activation of the T cell lymphoma, LBRM-33 and was distinct from other known B cell activators, notably IL-2 and IFN gamma. Biochemical purification of this activity indicated that it might be identical to granulocyte-macrophage colony stimulating factor (GM-CSF). The use of recombinant-derived GM-CSF protein unambiguously showed the role of this lymphokine in antibody production. These experiments demonstrated for the first time, the involvement of a hematopoietic factor in antigen-specific immune responses. Moreover, these results demonstrated an important regulatory circuit in the generation of antibody producing B cells in which GM-CSF, derived from activated T cells, stimulates macrophage function.
Grabstein
K
K
Immunex Corporation, Seattle, WA.
Mochizuki
D
D
Kronheim
S
S
Price
V
V
Cosman
D
D
Urdal
D
D
Gillis
S
S
Conlon
P
P
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D008222:Lymphokines; D011994:Recombinant Proteins; D003907:Dexamethasone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor