IL-21 dependent IgE production in human and mouse in vitro culture systems is cell density and cell division dependent and is augmented by IL-10.
IL-21 is known to enhance immunoglobulin production using human in vitro models. Using either PBMC or purified tonsilar B cells both stimulated with anti-CD40, IL-4+/-IL-21, this enhancement was shown to correlate with increased cell division especially for IgE and to a lesser extent for IgM and total IgG. Cell division was monitored by CFSE staining and maximum cell division was found at low initial cell plating densities. A correlation between increased cell division and IL-10-mediated enhancement of IgE production was also seen; however, increased cell division plays a smaller role with IL-10 than IL-21. This is further emphasized in that when IL-10 and IL-21 were added together there was a further synergistic increase in IgE seen, but no accompanying further increase in cell division. The mouse system was also examined for IL-21 effects as a function of cell concentration, and as in humans, IL-21 added to murine cells increased IgE production over IL-4/CD40 stimulated cells at lower cell concentrations; however, IL-21 significantly reduced IgE at higher plated cell concentrations.
Caven
Timothy H
TH
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298, USA. thcaven@hsc.vcu.edu
Shelburne
Anne
A
Sato
Jun
J
Chan-Li
Yee
Y
Becker
Steve
S
Conrad
Daniel H
DH
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D019013:CD40 Antigens / Q000276:immunology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002478:Cells, Cultured; D006801:Humans; D007072:Immunoglobulin D / Q000378:metabolism; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000096:biosynthesis; D007378:Interleukins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D000098546:Interleukin-21
D019013:CD40 Antigens; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D007378:Interleukins; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D000098546:Interleukin-21