Evidence for a critical role for IL-2 in CD40-mediated activation of naive B cells by primary CD4 T cells.
The interaction of CD40 on B cells with the CD40 ligand (CD40L) on preactivated CD4 T cells is critical for the initiation of T-dependent Ab responses. It is believed that signals via CD40 synergize with cytokines (e.g., IL-4 and IL-5) to drive B cell activation. However, primary T cells preactivated via CD3 alone cannot induce B cell proliferation; we have shown previously that costimulation of T cells via CD3 and CD28 stabilizes the expression of the CD40L, which we propose contributes to their capacity to act as competent helper-effector cells. Here we show that an additional, critical reason why CD3-stimulated CD40L-bearing T cells are incompetent helper cells is because they secrete insufficient IL-2. In contrast, CD28/CD3-activated T cells induce B cells to become IL-2 responsive via a combination of CD40L and IL-2-mediated signals, and these two stimuli subsequently drive B cell proliferation and IgM secretion. We therefore propose that T cells must first encounter Ag in conjunction with CD80/86 on APCs. This leads to the stable expression of CD40L and maximal secretion of IL-2, which together render primary T cells competent to activate B cells in an IL-2-dependent fashion.
Johnson-Léger
C
C
Division of Cellular Immunology, National Institute for Medical Research, London, United Kingdom.
Christenson
J R
JR
Holman
M
M
Klaus
G G
GG
D000818:Animals; D000917:Antibody Formation; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand; D018920:Coculture Techniques; D007075:Immunoglobulin M / Q000096:biosynthesis; D007376:Interleukin-2 / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology*; D008211:Lymphocyte Cooperation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018448:Models, Immunological; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; D017252:CD3 Complex; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D007075:Immunoglobulin M; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D023201:CD40 Ligand