Regulation of human B cell responsiveness by interferon-alpha: interferon-alpha-mediated suppression of B cell function is reversed through direct interactions between monocytes and B cells.
Previous studies have revealed that interferon-alpha (IFN-alpha) suppresses the B cell responses stimulated with Staphylococcus aureus (SA) + IL-2 in the complete absence of monocytes but enhances the responses of B cells contaminated with monocytes. The current studies therefore examined in detail the combined effects of IFN-alpha and monocytes on the B cell responses induced by SA + IL-2. Monocytes overcome the suppressive effects of IFN-alpha on the IgM production induced by SA + IL-2. Thus, in the presence of monocytes, IFN-alpha enhanced the IgM production by B cells stimulated with SA + IL-2. IFN-alpha still enhanced the IgM production induced by SA + IL-2 in the presence of monocytes and indomethacin. The IFN-alpha-mediated suppression of B cell responsiveness was not overcome by addition of factors generated from SA-activated monocytes, or any of IL-1 beta, IL-6, and TNF-alpha. Of note, the IFN-alpha-mediated suppression of B cell responsiveness was overcome only when B cells and monocytes were allowed to contact with each other. This reversal of the IFN-alpha-mediated suppression of B cell function was not blocked by any of the mAb to CD11a, CD18, CD54, or monomorphic determinants of HLA-DR. These results indicate that IFN-alpha enhances the B cell responses induced by SA + IL-2 through direct interactions between monocytes and B cells that do not involve lymphocyte-function-associated-1 molecules, intercellular adhesion molecule-1, or HLA-DR antigens. Thus, the data demonstrate the presence of unique direct interactions between B cells and monocytes that regulate human B cell responsiveness.
Oka
H
H
Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.
Hirohata
S
S
D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology; D007075:Immunoglobulin M / Q000096:biosynthesis; D016898:Interferon-alpha / Q000502:physiology*; D007376:Interleukin-2 / Q000276:immunology; D009000:Monocytes / Q000502:physiology*; D013211:Staphylococcus aureus / Q000276:immunology
D007075:Immunoglobulin M; D016898:Interferon-alpha; D007376:Interleukin-2