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Research paper thumbnail of CD40 ligand-positive CD8+ T cell clones allow B cell growth and differentiation

European Journal of Immunology, Oct 1, 1995

A fraction of activated CD8+ T cells expresses CD40 ligand (CD40L), a molecule that plays a key r... more A fraction of activated CD8+ T cells expresses CD40 ligand (CD40L), a molecule that plays a key role in T cell-dependent B cell stimulation. CD8+ T cell clones were examined for CD40L expression and for their capacity to allow the growth and differentiation of B cells, upon activation with immobilized anti-CD3. According to CD40L expression, CD8+ clones could be grouped into three subsets. CD8+ T cell clones expressing high levels of CD40L (> or = 80% CD40L+ cells) were equivalent to CD4+ T cell clones with regard to induction of tonsil B cell proliferation and immunoglobulin (Ig) production, provided the combination of interleukin (IL)-2 and IL-10 was added to cultures. CD8+ T cell clones, with intermediate levels of CD40L expression (10 to 30% CD40L+ cells), also stimulated B cell proliferation and Ig secretion with IL-2 and IL-10. B cell responses induced by these CD8+ T cell clones were neutralized by blocking monoclonal antibodies specific for either CD40L or CD40. By contrast, CD40L- T cell clones (< or = 5% CD40L+ cells), only induced marginal B cell responses even with IL-2 and IL-10. All three clone types were able to activate B cells as shown by up-regulation of CD25, CD80 and CD86 expression. A neutralizing anti-CD40L antibody indicated that T cell-dependent B cell activation was only partly dependent on CD40-CD40L interaction. These CD40L- clones had no inhibitory effects on B cell proliferation induced by CD40L-expressing CD8+ T cell clones. Taken together, these results indicate that CD8+ T cells can induce B cell growth and differentiation in a CD40L-CD40-dependent fashion.

Research paper thumbnail of Role of CD40 antigen and interleukin-2 in T cell-dependent human B lymphocyte growth

European Journal of Immunology, Feb 1, 1994

Research paper thumbnail of Role of cytokines in human B lymphocyte growth and differentiation

Nouvelle revue française d'hématologie, 1993

B lymphocytes express at their surface the CD40 antigen which belongs to the NGF receptor superfa... more B lymphocytes express at their surface the CD40 antigen which belongs to the NGF receptor superfamily. The crosslinking of the CD40 antigen using a mouse fibroblastic cell line expressing the human Fc receptor (Fc gamma RII/CDw32) and anti-CD40 monoclonal antibody induces resting B lymphocytes to enter a state of sustained proliferation. Addition of IL-4 to such cultures results in the generation of factor dependent long-term normal human B cell lines and in the secretion of IgE following isotype switching. Addition of IL-10 results in limited cell proliferation but most importantly in very high immunoglobulin production which results from the differentiation of B cells into plasma cells. The combination of IL-10 and TGF beta induces naive sIgD+ sIgM+ B cells to secrete IgA1 and IgA2 as a consequence of isotype switching. The extracellular domain of CD40 binds with high affinity and high specificity to a 32 kDa glycoprotein transiently expressed on activated T cells. This interactio...

Research paper thumbnail of CD40 ligand-positive CD8+ T cell clones allow B cell growth and differentiation

European Journal of Immunology, Oct 1, 1995

A fraction of activated CD8+ T cells expresses CD40 ligand (CD40L), a molecule that plays a key r... more A fraction of activated CD8+ T cells expresses CD40 ligand (CD40L), a molecule that plays a key role in T cell-dependent B cell stimulation. CD8+ T cell clones were examined for CD40L expression and for their capacity to allow the growth and differentiation of B cells, upon activation with immobilized anti-CD3. According to CD40L expression, CD8+ clones could be grouped into three subsets. CD8+ T cell clones expressing high levels of CD40L (> or = 80% CD40L+ cells) were equivalent to CD4+ T cell clones with regard to induction of tonsil B cell proliferation and immunoglobulin (Ig) production, provided the combination of interleukin (IL)-2 and IL-10 was added to cultures. CD8+ T cell clones, with intermediate levels of CD40L expression (10 to 30% CD40L+ cells), also stimulated B cell proliferation and Ig secretion with IL-2 and IL-10. B cell responses induced by these CD8+ T cell clones were neutralized by blocking monoclonal antibodies specific for either CD40L or CD40. By contrast, CD40L- T cell clones (< or = 5% CD40L+ cells), only induced marginal B cell responses even with IL-2 and IL-10. All three clone types were able to activate B cells as shown by up-regulation of CD25, CD80 and CD86 expression. A neutralizing anti-CD40L antibody indicated that T cell-dependent B cell activation was only partly dependent on CD40-CD40L interaction. These CD40L- clones had no inhibitory effects on B cell proliferation induced by CD40L-expressing CD8+ T cell clones. Taken together, these results indicate that CD8+ T cells can induce B cell growth and differentiation in a CD40L-CD40-dependent fashion.

Research paper thumbnail of Role of CD40 antigen and interleukin-2 in T cell-dependent human B lymphocyte growth

European Journal of Immunology, Feb 1, 1994

Research paper thumbnail of Role of cytokines in human B lymphocyte growth and differentiation

Nouvelle revue française d'hématologie, 1993

B lymphocytes express at their surface the CD40 antigen which belongs to the NGF receptor superfa... more B lymphocytes express at their surface the CD40 antigen which belongs to the NGF receptor superfamily. The crosslinking of the CD40 antigen using a mouse fibroblastic cell line expressing the human Fc receptor (Fc gamma RII/CDw32) and anti-CD40 monoclonal antibody induces resting B lymphocytes to enter a state of sustained proliferation. Addition of IL-4 to such cultures results in the generation of factor dependent long-term normal human B cell lines and in the secretion of IgE following isotype switching. Addition of IL-10 results in limited cell proliferation but most importantly in very high immunoglobulin production which results from the differentiation of B cells into plasma cells. The combination of IL-10 and TGF beta induces naive sIgD+ sIgM+ B cells to secrete IgA1 and IgA2 as a consequence of isotype switching. The extracellular domain of CD40 binds with high affinity and high specificity to a 32 kDa glycoprotein transiently expressed on activated T cells. This interactio...

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