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Interaction between CD40 on B cells and CD40 ligand molecules on T cells is pivotal for the generation of a thymus-dependent antibody response. Here we show that B cells deficient in CD40 expression are unable to elicit the proliferation of allogeneic T cells in vitro. More importantly, mice immunized with CD40-/- B cells become tolerant to allogeneic major histocompatibility complex (MHC) antigens as measured by a mixed lymphocyte reaction and cytotoxic T-cell assay. The failure of CD40-/- B cells to serve as antigen presenting cells in vitro was corrected by the addition of anti-CD28 mAb. Moreover, lipopolysaccharide stimulation, which upregulates B7 expression, reversed the inability of CD40-/- B cells to stimulate an alloresponse in vitro and abrogated the capacity of these B cells to induce tolerance in vivo. These results suggest that CD40 engagement by CD40 ligand expressed on antigen-activated T cells is critical for the upregulation of B7 molecules on antigen-presenting B cells that subsequently deliver the costimulatory signals necessary for T-cell proliferation and differentiation. Our experiments suggest a novel strategy for the induction of antigen-specific tolerance in vivo.

Original publication

DOI

10.1073/pnas.93.10.4994

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

14/05/1996

Volume

93

Pages

4994 - 4998

Keywords

Animals, Antigens, CD, B-Lymphocytes, B7-1 Antigen, B7-2 Antigen, CD40 Antigens, CD40 Ligand, Immune Tolerance, In Vitro Techniques, Isoantigens, Ligands, Lymphocyte Activation, Lymphocyte Cooperation, Lymphocyte Culture Test, Mixed, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, T-Lymphocytes