title: Antigen-specific B cells preferentially induce CD4+ T cells to produce IL-4.
abstract: The role of Ag presentation by B cells in regulating the development of T cells with restricted cytokine profiles remains controversial. In this report, we compared Ag presentation by naive polyclonal B cells, naive Ag-specific B cells (from Ig receptor transgenic mice), or splenic adherent cells (SAC) and examined the capacity of these cells to influence cytokine production by CD4+ T cells. Freshly isolated naive B cells stimulated vigorous T cell proliferation and very strong T cell cytokine responses, but only when cultured with Ag recognized by the B cell Ig receptor (cognate Ag) and not when cultured with a noncognate Ag. Under these conditions, B cells activated by Ig receptor-mediated endocytosis of Ag induced both naive and Ag-primed CD4+ T cells to produce high levels of IL-4 (300-4000 pg/ml). In contrast, SAC induced the production of very low levels of IL-4 (<100 pg/ml) but much higher maximal levels of IFN-gamma than did Ag-specific B cells. The induction of IL-4 synthesis by Ag-specific B cells was significantly reduced by blocking CD40-CD40 ligand (CD40L) interactions or by the addition of small quantities of rIL-12. These results suggest that B cells activated by their cognate Ag preferentially induce IL-4 synthesis as a result of the interaction of CD40L on T cells with CD40, whereas SAC preferentially induce IFN-gamma synthesis by T cells as a result of their greater production of IL-12 and their limited capacity to trigger CD40L on T cells.
authors.affiliation: Department of Pediatrics, Stanford University, CA 94305, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Macaulay
authors.forename: R H
authors.initials: RH
authors.lastname: DeKruyff
authors.forename: C C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: D T
authors.initials: DT
authors.lastname: Umetsu
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand; D005260:Female; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis*; D008024:Ligands; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D008024:Ligands; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D023201:CD40 Ligand; D018664:Interleukin-12; D015847:Interleukin-4; D010047:Ovalbumin