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Correlation of anti-viral B cell responses and splenic morphology with expression of B cell-specific molecules

Fehr, Thomas ; López-Macías, Constantino ; Odermatt, Bernhard ; Torres, Raul M. ; Schubart, Daniel B. ; O'Keefe, Theresa L. ; Matthias, Patrick ; Hengartner, Hans ; Zinkernagel, Rolf M.

In: International Immunology, 2000, vol. 12, no. 9, p. 1275-1284

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    Titre
    • Correlation of anti-viral B cell responses and splenic morphology with expression of B cell-specific molecules
    Auteur
    • Fehr, Thomas. Institute of Experimental Immunology, Department of Pathology, University Hospital, Schmelzbergstrasse 12, 8091 Zürich, Switzerland
    • López-Macías, Constantino. Institute of Experimental Immunology, Department of Pathology, University Hospital, Schmelzbergstrasse 12, 8091 Zürich, Switzerland
    • Odermatt, Bernhard. Institute of Experimental Immunology, Department of Pathology, University Hospital, Schmelzbergstrasse 12, 8091 Zürich, Switzerland
    • Torres, Raul M.
    • Schubart, Daniel B.. Friedrich Miescher Institute, Maulbeerstrasse 66, 4058 Basel, Switzerland
    • O'Keefe, Theresa L.. Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    • Matthias, Patrick. Friedrich Miescher Institute, Maulbeerstrasse 66, 4058 Basel, Switzerland
    • Hengartner, Hans. Institute of Experimental Immunology, Department of Pathology, University Hospital, Schmelzbergstrasse 12, 8091 Zürich, Switzerland
    • Zinkernagel, Rolf M.. Institute of Experimental Immunology, Department of Pathology, University Hospital, Schmelzbergstrasse 12, 8091 Zürich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • International Immunology, 2000, vol. 12, no. 9, p. 1275-1284. Oxford University Press
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:290508
    Summary
    This study attempted to evaluate and compare the role of various B cell-specific markers for anti-viral immune responses in mouse strains lacking molecules belonging to the B cell receptor (BCR) complex (IgM, Igα and Cκ), the co-stimulatory molecules (CD19 and CD22), the protein kinases [Bruton's tyrosine kinase (Btk)] or the transcription factors (OBF-1). These mice were tested in two model infections [vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV)] using T cell-independent (TI) or T cell-dependent (TD) antigens. All mice controlled an LCMV infection indicating that cytotoxic T cell functions were within normal ranges. In contrast, OBF-1-/- mice were partially protected and mb-1Δc/Δc mice not at all protected against VSV infection, a virus that is controlled virtually exclusively by neutralizing antibodies. Susceptibility to VSV infection was correlated with structural defects in the spleen: absence of mature B cells and follicles with marginal zone macrophages and absence of germinal centers with follicular dendritic cells correlated with lack or substantial reduction of protective IgM and IgG responses respectively. The lack of κ light chain did not affect the neutralizing response, indicating that it could easily be replaced by the λ chain. Absence of the co-stimulatory molecules CD19 and CD22 or of the signaling molecule Btk had modulating effects, but did not increase susceptibility to VSV or LCMV. Our findings suggest that there are crucial molecules for B cell activation at the beginning (BCR complex) and the end (transcription) of the signaling cascade, whereas fine-tuning factors modulating the response in between exhibit considerable functional overlap