Effects of IL-4, IL-5, and IL-6 on growth and immunoglobulin production of Epstein-Barr virus-infected human B cells.
In the present study we investigated whether interleukin-4 (IL-4), IL-5, and IL-6 could enhance the efficiency of Epstein-Barr virus (EBV) transformation for the generation of specific human monoclonal antibody (HuMAb)-producing B-cell lines directed against erythrocyte Rhesus(D) antigen. In newly EBV-infected B cells, IL-4 and IL-6 caused a comparable enhancement of proliferation and of total IgG and IgA production. IL-6 showed a much stronger effect than IL-4 on IgM production, whereas IL-4 was unique in inducing IgE production. No stimulatory effects of IL-5 on either growth or Ig production were observed. Although addition of IL-6 resulted during the early phase after EBV infection in high numbers of Ag-specific antibody-producing wells, this did not result in an increased number of stable HuMAb-secreting cell lines. When the effects of cytokines were tested on established polyclonal EBV B cells, in a high cell density culture system, only IL-6 was able to enhance Ig secretion, while no effect could be demonstrated on proliferation. These studies substantiate that IL-6 is an important regulator of proliferation and Ig production, and that it acts at distinct stages after EBV infection, but does not increase the final overall recovery of Ag-specific EBV B-cell lines.
Bende
R J
RJ
Department of Hybridoma and Tissue Culture, The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Jochems
G J
GJ
Frame
T H
TH
Klein
M R
MR
van Eijk
R V
RV
van Lier
R A
RA
Zeijlemaker
W P
WP
D000917:Antibody Formation / Q000187:drug effects*; D000956:Antigens, Viral / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000382:microbiology*; D002455:Cell Division / Q000187:drug effects; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D019309:Epstein-Barr Virus Nuclear Antigens; D004854:Herpesvirus 4, Human; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007518:Isoantibodies / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D012204:Rh-Hr Blood-Group System / Q000276:immunology; D013997:Time Factors
D000956:Antigens, Viral; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; D007132:Immunoglobulin Isotypes; D015848:Interleukin-5; D015850:Interleukin-6; D007518:Isoantibodies; D012204:Rh-Hr Blood-Group System; D015847:Interleukin-4