B lymphocytes as antigen-presenting cells for CD4+ T cell priming in vivo.
The contribution of B lymphocytes as APCs for CD4+ T cell priming remains controversial, based on findings that B cells cannot provide the requisite ligating and costimulatory signals for naive T cells to be activated. In the current study, we have examined Ag-specific T:B cell collaboration under circumstances in which B cells take up Ag through Ig receptors in vivo. This results in their activation and an ability to effectively stimulate naive CD4+ T cells both in vitro and in vivo. The aim of this work was to establish some of the key molecular interactions, as well as kinetics, between Ag-specific T and B cells that enable this priming to take place. Our approach was to amplify the starting pools of both Ag-specific T and B cell populations in vivo to track directly the events during initial T:B cell collaborations. We show that the induction of optimal levels of T cell priming to a protein Ag requires the involvement of Ag-specific B cells. The interaction that results between Ag-specific T and B cells prevents the down-modulation of B7 costimulatory molecules usually observed in the absence of appropriate T cells. Moreover, this prevention in down-modulation is independent of CD40:CD40 ligand contact. Finally, we present data suggesting that once Ag-specific T and B cells interact, there is a rapid (1-2-h) down-regulation of antigenic complexes on the surface of the B lymphocytes, possibly to prevent them from engaging other T cells in the vicinity and therefore focus the initial interaction.
Constant
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SL
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA. stephanie.constant@yale.edu
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D023201:CD40 Ligand; D005452:Fluoresceins; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008822:Mice, Transgenic; D009113:Muramidase / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D011961:Receptors, Fc; D013388:Succinimides; D013997:Time Factors; D015854:Up-Regulation
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D018122:B7-1 Antigen; D018106:CD28 Antigens; D005452:Fluoresceins; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D013388:Succinimides; D023201:CD40 Ligand; D009113:Muramidase