The acquisition of cytokine responsiveness by murine B cells: a role for antigen and IL-5 in the induction of IL-2 receptors.
The mechanism whereby small resting (high buoyant density) murine B cells are induced to express interleukin-2 receptors (IL-2R) and to respond to IL-2 was addressed by staining with anti-IL-2R alpha and -IL-2R beta monoclonal antibodies (mAb), and using receptor-specific cDNA probes. Resting B cells expressed undetectable levels of both IL-2R alpha and beta chains on their surface and did not respond to IL-2, even at supra-physiological concentrations. Sepharose-coupled, but not streptavidin-cross-linked, plastic-adsorbed or soluble, anti-mu up-regulated the expression of IL-2R alpha and beta chains and mRNA to levels comparable to those seen in activated T cells. Anti-mu-stimulated B cells responded to IL-2 by incorporation of [3H]thymidine and high rate immunoglobulin (Ig) secretion. Both IL-5 (at optimal concentration) and suboptimal lipopolysaccharide (LPS; 20 ng/ml) induced surface expression of IL-2R alpha. The level of expression induced by IL-5 was equivalent to that on anti-Ig-activated B cells. Neither stimulus induced detectable expression of IL-2R beta, and neither induced B cells to respond to IL-2. IL-2R alpha expression was strongly enhanced, and low levels of IL-2R beta staining and mRNA were induced by the combination of LPS plus IL-5. LPS+IL-5-treated B cells responded to IL-2 by Ig secretion. This indicates that B cells regulate their responsiveness to IL-2 similarly to T cells, via the combined level of expression of IL-2R beta and IL-2R alpha. The synergy between IL-5 and LPS for B-cell responses shows a requirement for complementary stimuli such as would be provided by cytokines, and either cellular interaction or antigen recognition in regulation of B-cell responsiveness to IL-2.
Poudrier
J
J
Department of Medicine, McGill University, Montreal, Quebec, Canada.
Owens
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D007376:Interleukin-2 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology
D007376:Interleukin-2; D015848:Interleukin-5; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D015375:Receptors, Interleukin-2