Lymphotoxin α1β2 expression on B cells is required for follicular dendritic cell activation during the germinal center response

• Published in: European journal of immunology 2013-02, Vol.43 (2), p.348-359
• Main Authors: Myers, Riley C., King, R. Glenn, Carter, Robert H., Justement, Louis B.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD19 - biosynthesis; Antigens, CD19 - genetics; Antigens, CD19 - immunology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; CD19; Dendritic Cells, Follicular - immunology; Dendritic Cells, Follicular - metabolism; Follicular dendritic cell; Germinal center; Germinal Center - immunology; Germinal Center - metabolism; Lymphocyte Activation; Lymphotoxin alpha1, beta2 Heterotrimer - biosynthesis; Lymphotoxin alpha1, beta2 Heterotrimer - genetics; Lymphotoxin alpha1, beta2 Heterotrimer - immunology; Membrane lymphotoxin; Mice; Mice, Inbred C57BL; Receptors, IgG - biosynthesis; Receptors, IgG - genetics; Receptors, IgG - immunology; Up-Regulation; Vascular Cell Adhesion Molecule-1 - biosynthesis; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - immunology
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201242471

CD19‐deficient mice were used as a model to study follicular dendritic cell (FDC) activation because these mice have normal numbers of FDC‐containing primary follicles, but lack the ability to activate FDCs or form GCs. It was hypothesized that CD19 expression is necessary for B‐cell activation and upregulation of membrane lymphotoxin (mLT) expression, which promotes FDC activation. Using VCAM‐1 and FcγRII/III as FDC activation markers, it was determined that the adoptive transfer of CD19+ wild‐type B cells into CD19‐deficient hosts rescued GC formation and FDC activation, demonstrating that CD19 expression on B cells is required for FDC activation. In contrast, CD19+ donor B cells lacking mLT were unable to induce VCAM‐1 expression on FDCs, furthermore FcγRII/III upregulation was impaired in FDCs stimulated with mLT‐deficient B cells. VCAM‐1 expression on FDCs, but not FcγRII/III, was rescued when CD19‐deficient B cells expressing transgenic mLT were cotransferred into recipient mice with CD19+, mLT‐deficient B cells, suggesting that FDC activation requires the CD19‐dependent upregulation of mLT on activated B cells. Collectively, these data demonstrate that activated B cells are responsible for the initiation of FDC activation resulting in a microenvironment supportive of GC development and maintenance.