Human recombinant erythropoietin directly stimulates B cell immunoglobulin production and proliferation in serum-free medium.
The effect of human recombinant erythropoietin (Epo) on B cell responses was studied in a serum-free medium. Epo enhanced IgM production and thymidine uptake by a human IgM-producing lymphoblastoid cell line, CBL. This effect was specific to Epo since enhancement was blocked by anti-Epo antibody but not by control antibody. Among the various cytokines, interleukin-4 (IL-4) enhanced IgM production and thymidine uptake while IL-6 enhanced IgM production without affecting thymidine uptake. In contrast, other cytokines including IL-1 beta, IL-2, IL-5, interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), or granulocyte/macrophage colony-stimulating factor (GM-CSF) were without effect. However, the enhancing effect of Epo is different from that of IL-4 or IL-6, since Epo effect was not blocked by anti-IL-4 antibody or anti-IL-6 antibody. Moreover, specific binding of Epo was detected on CBL cells. Epo also enhanced immunoglobulin (IgG, IgM and IgA) production and thymidine uptake by purified tonsil small resting B cells stimulated by Staphylococcus aureus Cowan strain I (SAC) or by large activated B cells. In contrast, Epo had no effect on unstimulated small resting B cells. These results indicate that Epo could directly stimulate activated and differentiated B cells and could enhance B cell immunoglobulin production and proliferation.
Kimata
H
H
Department of Paediatrics, Faculty of Medicine, Kyoto University Hospital, Japan.
Yoshida
A
A
Ishioka
C
C
Masuda
S
S
Sasaki
R
R
Mikawa
H
H
D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001667:Binding, Competitive; D003470:Culture Media; D016207:Cytokines / Q000494:pharmacology; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000378:metabolism; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D003470:Culture Media; D016207:Cytokines; D007075:Immunoglobulin M; D011956:Receptors, Cell Surface; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D013936:Thymidine