Th1 and Th2 help for B cells: differential capacity for induction of autonomous responsiveness to IL-2.
Sustained interaction with Th1 cells has been shown to induce IL-2 responsiveness by murine B cells. This is equivalently dependent on CD40, CD54/ICAM-1 and MHC II ligation, and co-cross-linking of CD54 and MHC II in the presence of IL-5 up-regulates a functional IL-2R on B cells. We now show that IL-5 (125 U/ml) synergizes with Th1 cells to induce B cell responses to IL-2, that are maintained following T-cell removal, e.g. autonomous. Th1 help in the absence of IL-5 resulted in weak or undetectable responses following T cell removal. The mechanism of IL-5 synergy involved persistence of IL-2R beta expression following T cell removal, as opposed to enhancement of IL-2R induction or function. The level of contact-induced IL-2R expression on B cells was not itself modified by IL-5. The effects of IL-5 did not overcome the requirement for T contact signals and treatment of B cells with soluble anti-Ig did not circumvent the need for IL-5 for autonomous IL-2 responses. Consistent with the above, interaction with an IL-5-producing Th2 clone induced strong autonomous B cell responses to IL-2. Qualitative differences of Th2 help over that of Th1 may thus be attributable to their differential ability to induce autonomous B cell responsiveness to cytokines. This may be representative of events in which maintenance of cell cycle is important, as is the case in germinal centers.
Poudrier
J
J
Department of Medicine, McGill University, Montréal, Québec, Canada.
Owens
T
T
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D007376:Interleukin-2 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011947:Receptors, Antigen, B-Cell / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D007376:Interleukin-2; D015848:Interleukin-5; D011947:Receptors, Antigen, B-Cell; D015375:Receptors, Interleukin-2