Individuals with X-linked hyper-IgM syndrome fail to express functional CD40 ligand (CD40L) and, as a consequence, are incapable of mounting protective antibody responses to opportunistic bacterial infections. To address the role of CD40L in humoral immunity, we created, through homologous recombination, mice deficient in CD40L expression. These mice exhibited no gross developmental deficiencies or health abnormalities and contained normal percentages of B and T cell subpopulations. CD40L-deficient mice did display selective deficiencies in humoral immunity; basal serum isotype levels were significantly lower than observed in normal mice, and IgE was undetectable. Furthermore, the CD40L-deficient mice failed to mount secondary antigen-specific responses to immunization with a thymus-dependent antigen, trinitrophenol-conjugated keyhole limpet hemocyanin (TNP-KLH). By contrast, the CD40L-deficient mice produced antigen-specific antibody of all isotypes except IgE in response to the thymus-independent antigen, DNP-Ficoll. These results underscore the requirement of CD40L for T cell-dependent antibody responses. Moreover, Ig class switching to isotypes other than IgE can occur in vivo in the absence of CD40L, supporting the notion that alternative B cell signaling pathways regulate responses to thymus-independent antigens.
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1 November 1994
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November 01 1994
Humoral immune responses in CD40 ligand-deficient mice.
B R Renshaw,
B R Renshaw
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
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W C Fanslow, 3rd,
W C Fanslow, 3rd
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
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R J Armitage,
R J Armitage
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
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K A Campbell,
K A Campbell
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
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D Liggitt,
D Liggitt
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
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B Wright,
B Wright
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
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B L Davison,
B L Davison
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
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C R Maliszewski
C R Maliszewski
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
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B R Renshaw
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
W C Fanslow, 3rd
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
R J Armitage
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
K A Campbell
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
D Liggitt
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
B Wright
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
B L Davison
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
C R Maliszewski
Department of Molecular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1994) 180 (5): 1889–1900.
Citation
B R Renshaw, W C Fanslow, R J Armitage, K A Campbell, D Liggitt, B Wright, B L Davison, C R Maliszewski; Humoral immune responses in CD40 ligand-deficient mice.. J Exp Med 1 November 1994; 180 (5): 1889–1900. doi: https://doi.org/10.1084/jem.180.5.1889
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