B cell response to fresh and effector T helper cells. Role of cognate T-B interaction and the cytokines IL-2, IL-4, and IL-6.
The helper activity of resting T cells and in vitro generated effector T cells and the relative roles of cognate interaction, diffusible cytokines, and non-cognate T-B contact in B cell antibody responses were evaluated in a model in which normal murine CD4+ T cells (Th), activated with alloantigen-bearing APC, were used to support the growth and differentiation of unstimulated allogeneic B cells. Both "fresh" T cells, consisting of memory and naive cells, stimulated for 24 h, and "effector" T cells, derived from naive cells after 4 days of in vitro stimulation, induced the secretion of IgM, IgG3, IgG1, IgG2a, and IgA. Effector T cells were significantly better helpers of the response of small dense B cells, inducing Ig at lower numbers and inducing at optimal numbers 2- to 3-fold more Ig production than fresh T cells. The predominant isotype secreted was IgM. Supernatants derived from fresh T cell cultures contained moderate levels of IL-2, whereas those from effector cultures contained significant levels of IL-6 and IFN-gamma in addition to IL-2. The involvement of soluble factors in the B cell response was demonstrated by the ability of antibodies to the cytokines IL-2, IL-4, and IL-6 to each block Ig secretion. Antibodies to IL-5 and IFN-gamma had no effect on the T cell-induced response. Kinetic studies suggested that IL-4 acted during the initial stages of the response, whereas the inability of anti-IL-6 to block B cell proliferation suggested that IL-6 was involved in part in promoting differentiation of the B cells. The relative contributions of cognate (MHC-restricted) and bystander (MHC-unrestricted) T-B cell contact vs cytokine (non-contact)-mediated responses were assessed in a transwell culture system. The majority of the IgM, IgG3, IgG1, and IgG2a response induced by both fresh and effector T cells was dependent on cognate interaction with small, high density B cells. In contrast, a small proportion of these isotypes and most of the IgA secreted resulted from the action of IL-6 on large, presumably preactivated, B cells. The IgA response did not require cell contact or vary when fresh and effector cells were the helpers. The contribution of bystander contact in the overall antibody response to both T cell populations was minimal.(ABSTRACT TRUNCATED AT 400 WORDS)
Croft
M
M
Department of Biology, University of California, San Diego, La Jolla 92093-0063.
Swain
S L
SL
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002450:Cell Communication; D002454:Cell Differentiation; D002478:Cells, Cultured; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D007371:Interferon-gamma / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D007132:Immunoglobulin Isotypes; D007376:Interleukin-2; D015850:Interleukin-6; D007519:Isoantigens; D015847:Interleukin-4; D007371:Interferon-gamma