Effect of IL-2 on immunoglobulin production by anti-CD40-activated human B cells: synergistic effect with IL-10 and antagonistic effect with IL-4.
Activation of B cells by anti-CD40 provides an excellent model to investigate the direct effect of various cytokines on Ig production. Using this culture system, we examined the effect of IL-2 alone or in combination with other cytokines. IL-2 alone had only a moderate effect on Ig production by anti-CD40-activated B cells if compared with the effect of IL-10. However, IL-2 significantly augmented the synthesis of IgM, IgA, and IgG, including all IgG subclasses by anti-CD40-activated B cells cultured in the presence of IL-10. Both IgD- and IgD+ B cells showed an increase of IL-10-induced Ig production if IL-2 was added to the culture. The addition of IL-2 also increased immunoglobulin synthesis by anti-CD40/IL-10-activated B cells from patients with common variable immunodeficiency (CVI) and defective IL-2 production, suggesting that in a subgroup of CVI patients the IL-2 deficiency may contribute to the observed hypogammaglobulinemia. In contrast, the addition of IL-2 had a suppressive effect on IgE and IgG4 production by B cells cultured in the presence of anti-CD40 and IL-4. These data demonstrate that IL-2 plays an active role in the regulation of Ig production via CD40 by anti-CD40-activated B cells.
Nonoyama
S
S
Department of Pediatrics, University of Washington, Seattle 98195.
Farrington
M L
ML
Ochs
H D
HD
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D019013:CD40 Antigens; D002478:Cells, Cultured; D017074:Common Variable Immunodeficiency / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D016753:Interleukin-10 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D007132:Immunoglobulin Isotypes; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4