Generation of B cell memory and affinity maturation. Induction with Th1 and Th2 T cell clones.
We used an adoptive transfer system and CD4+ T cell clones with defined lymphokine profiles to examine the role of CD4+ T cells and the types of lymphokines involved in the development of B cell memory and affinity maturation. Keyhole limpet hemocyanin (KLH)-specific CD4+ Th2 clones (which produce IL-4 and IL-5 but not IL-2 or IFN-gamma) were capable of inducing B cell memory and affinity maturation, after transfer into nude mice or after transfer with unprimed B cells into irradiated recipients and immunization with TNP-KLH. In addition, KLH-specific Th1 clones, which produce IL-2 and IFN-gamma but not IL-4 or IL-5, were also effective in inducing B cell memory and high affinity anti-TNP-specific antibody. The induction of affinity maturation by Th1 clones occurred in the absence of IL-4, as anti-IL-4 mAb had no effect on the affinity of the response whereas anti-IFN-gamma mAb completely blocked the response. Th1 clones induced predominantly IgG2a and IgG3 antibody, although Th2 clones induced predominantly IgG1 and IgE antibody. We thus demonstrated that some Th1 as well as some Th2 clones can function in vivo to induce Ig synthesis. These results also suggest that a single type of T cell with a restricted lymphokine profile can induce both the terminal differentiation of B cells into antibody secreting cells as well as induce B cell memory and affinity maturation. Moreover, these results suggest that B cell memory and affinity maturation can occur either in the presence of Th2 clones secreting IL-4 but not IFN-gamma, or alternatively in the presence of Th1 clones secreting IFN-gamma but not IL-4.
Department of Pediatrics, Stanford University, CA 94305.
L V
LV
Rizzo
R H
RH
DeKruyff
D T
DT
Umetsu
D000818:Animals; D000915:Antibody Affinity; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D007116:Immunization, Passive; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology; D008222:Lymphokines / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D007376:Interleukin-2; D015848:Interleukin-5; D008222:Lymphokines; D015847:Interleukin-4; D007371:Interferon-gamma