Interferon-gamma regulation of B lymphocyte differentiation: activation of B cells is a prerequisite for IFN-gamma-mediated inhibition of B cell differentiation.
The Th1 and NK cell-derived cytokine interferon-gamma (IFN-gamma) influences both immune and inflammatory responses, and under some circumstances, IFN-gamma can inhibit B cell differentiation. We found that IFN-gamma inhibited LPS-induced IgM production in B cells by reducing the precursor frequency of IgM-secreting cells. This occurred without a significant decrease in B cell proliferation in response to either LPS or F(ab')2 anti-IgM. We also found that IFN-gamma inhibited IgM secretion, even when added as late as 48 hr after LPS stimulation. Small resting B cells were not affected by a pulse with IFN-gamma. However, a pulse of IFN-gamma inhibited the response of activated B cells to subsequent stimulation with LPS. Also, LPS upregulated expression of the IFN-gamma receptor on B cells. Our studies show that IFN-gamma targets stimulated but not resting B cells and suggest that IFN-gamma plays an important role in the normal homeostatic control of B cell polyclonal responses.
Abed
N S
NS
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Chace
J H
JH
Fleming
A L
AL
Cowdery
J S
JS
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D005260:Female; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D011917:Rats, Inbred Lew; D017471:Receptors, Interferon / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation; D000096743:Interferon gamma Receptor
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; D007371:Interferon-gamma; D008070:Lipopolysaccharides; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor