Evidence for a critical role for IL-2 in CD40-mediated activation of naive B cells by primary CD4 T cells
| Autor: | C, Johnson-Léger, J R, Christenson, M, Holman, G G, Klaus |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
CD4-Positive T-Lymphocytes
Antigen Presentation Membrane Glycoproteins CD3 Complex CD40 Ligand Lymphocyte Cooperation Models Immunological Lymphocyte Activation Coculture Techniques Specific Pathogen-Free Organisms Mice Inbred C57BL Mice CD28 Antigens Immunoglobulin M Antigens CD Antibody Formation B7-1 Antigen Mice Inbred CBA Animals Interleukin-2 B7-2 Antigen CD40 Antigens Signal Transduction |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 161(9) |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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