J. Exp. Med., Volume 188, Number 1, July 1, 1998 145-155

Antiviral Protection and Germinal Center Formation, But Impaired B Cell Memory in the Absence of CD19

By Thomas Fehr,^* Robert C. Rickert, Bernhard Odermatt,^* Jürgen Roes, Klaus Rajewsky, Hans Hengartner,^* and Rolf M. Zinkernagel^*

From the ^* Institute of Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland; and the  Institute for Genetics, University of Cologne, D-50931 Cologne, Germany

Coligation of CD19, a molecule expressed during all stages of B cell development except plasmacytes, lowers the threshold for B cell activation with anti-IgM by a factor of 100. The cytoplasmic tail of CD19 contains nine tyrosine residues as possible phosphorylation sites and is postulated to function as the signal transducing element for complement receptor (CR)2. Generation and analysis of CD19 gene-targeted mice revealed that T cell-dependent (TD) antibody responses to proteinaceous antigens were impaired, whereas those to T cell-independent (TI) type 2 antigens were normal or even augmented. These results are compatible with earlier complement depletion studies and the postulated function of CD19. To analyze the role of CD19 in antiviral antibody responses, we immunized CD19^/ mice with viral antigens of TI-1, TI-2, and TD type. The effect of CD19 on TI responses was more dependent on antigen dose and replicative capacity than on antigen type. CR blocking experiments confirmed the role of CD19 as B cell signal transducer for complement. In contrast to immunization with protein antigens, infection of CD19^/ mice with replicating virus led to generation of specific germinal centers, which persisted for >100 d, whereas maintenance of memory antibody titers as well as circulating memory B cells was fully dependent on CD19. Thus, our study confirms a costimulatory role of CD19 on B cells under limiting antigen conditions and indicates an important role for B cell memory.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Fink, K., Manjarrez-Orduno, N., Schildknecht, A., Weber, J., Senn, B. M., Zinkernagel, R. M., Hengartner, H. (2007). B Cell Activation State-Governed Formation of Germinal Centers following Viral Infection. J. Immunol. 179: 5877-5885 [Abstract] [Full Text]  
• van Zelm, M. C., Reisli, I., van der Burg, M., Castano, D., van Noesel, C. J.M., van Tol, M. J.D., Woellner, C., Grimbacher, B., Patino, P. J., van Dongen, J. J.M., Franco, J. L. (2006). An antibody-deficiency syndrome due to mutations in the CD19 gene.. NEJM 354: 1901-1912 [Abstract] [Full Text]  
• Del Nagro, C. J., Kolla, R. V., Rickert, R. C. (2005). A Critical Role for Complement C3d and the B Cell Coreceptor (CD19/CD21) Complex in the Initiation of Inflammatory Arthritis. J. Immunol. 175: 5379-5389 [Abstract] [Full Text]  
• Huber, C., Thielen, C., Seeger, H., Schwarz, P., Montrasio, F., Wilson, M. R., Heinen, E., Fu, Y.-X., Miele, G., Aguzzi, A. (2005). Lymphotoxin-{beta} Receptor-Dependent Genes in Lymph Node and Follicular Dendritic Cell Transcriptomes. J. Immunol. 174: 5526-5536 [Abstract] [Full Text]  
• Brooks, S. R., Kirkham, P. M., Freeberg, L., Carter, R. H. (2004). Binding of Cytoplasmic Proteins to the CD19 Intracellular Domain Is High Affinity, Competitive, and Multimeric. J. Immunol. 172: 7556-7564 [Abstract] [Full Text]  
• Song, H., Cerny, J. (2003). Functional Heterogeneity of Marginal Zone B Cells Revealed by Their Ability to Generate Both Early Antibody-forming Cells and Germinal Centers with Hypermutation and Memory in Response to a T-dependent Antigen. J. Exp. Med. 198: 1923-1935 [Abstract] [Full Text]  
• Otero, D. C., Anzelon, A. N., Rickert, R. C. (2003). CD19 Function in Early and Late B Cell Development: I. Maintenance of Follicular and Marginal Zone B Cells Requires CD19-Dependent Survival Signals. J. Immunol. 170: 73-83 [Abstract] [Full Text]  
• Nielsen, C. H., Leslie, R. G. Q. (2002). Complement's participation in acquired immunity. J. Leukoc. Biol. 72: 249-261 [Abstract] [Full Text]  
• Warnatz, K., Denz, A., Drager, R., Braun, M., Groth, C., Wolff-Vorbeck, G., Eibel, H., Schlesier, M., Peter, H. H. (2002). Severe deficiency of switched memory B cells (CD27+IgM-IgD-) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood 99: 1544-1551 [Abstract] [Full Text]  
• Ochsenbein, A. F., Pinschewer, D. D., Sierro, S., Horvath, E., Hengartner, H., Zinkernagel, R. M. (2000). Protective long-term antibody memory by antigen-driven and T help-dependent differentiation of long-lived memory B cells to short-lived plasma cells independent of secondary lymphoid organs. Proc. Natl. Acad. Sci. USA 10.1073/pnas.230417497v1 [Abstract] [Full Text]  
• Fehr, T., Lopez-Macias, C., Odermatt, B., Torres, R. M., Schubart, D. B., O'Keefe, T. L., Matthias, P., Hengartner, H., Zinkernagel, R. M. (2000). Correlation of anti-viral B cell responses and splenic morphology with expression of B cell-specific molecules. Int Immunol 12: 1275-1284 [Abstract] [Full Text]  
• Macpherson, A. J., Gatto, D., Sainsbury, E., Harriman, G. R., Hengartner, H., Zinkernagel, R. M. (2000). A Primitive T Cell-Independent Mechanism of Intestinal Mucosal IgA Responses to Commensal Bacteria. Science 288: 2222-2226 [Abstract] [Full Text]  
• Smith, K. G.C., Light, A., O'Reilly, L. A., Ang, S.-M., Strasser, A., Tarlinton, D. (2000). bcl-2 Transgene Expression Inhibits Apoptosis in the Germinal Center and Reveals Differences in the Selection of Memory B Cells and Bone Marrow Antibody-forming Cells. J. Exp. Med. 191: 475-484 [Abstract] [Full Text]  
• Ochsenbein, A. F., Fehr, T., Lutz, C., Suter, M., Brombacher, F., Hengartner, H., Zinkernagel, R. M. (1999). Control of Early Viral and Bacterial Distribution and Disease by Natural Antibodies. Science 286: 2156-2159 [Abstract] [Full Text]  
• Mahmoud, M. S., Fujii, R., Ishikawa, H., Kawano, M. M. (1999). Enforced CD19 Expression Leads to Growth Inhibition and Reduced Tumorigenicity. Blood 94: 3551-3558 [Abstract] [Full Text]  
• Da Costa, X. J., Brockman, M. A., Alicot, E., Ma, M., Fischer, M. B., Zhou, X., Knipe, D. M., Carroll, M. C. (1999). Humoral response to herpes simplex virus is complement-dependent. Proc. Natl. Acad. Sci. USA 96: 12708-12712 [Abstract] [Full Text]  
• Ochsenbein, A. F., Pinschewer, D. D., Odermatt, B., Carroll, M. C., Hengartner, H., Zinkernagel, R. M. (1999). Protective T Cell-independent Antiviral Antibody Responses Are Dependent on Complement. J. Exp. Med. 190: 1165-1174 [Abstract] [Full Text]  
• Bachmann, M. F., Zinkernagel, R. M., Oxenius, A. (1998). Cutting Edge Commentary: Immune Responses in the Absence of Costimulation: Viruses Know the Trick. J. Immunol. 161: 5791-5794 [Abstract] [Full Text]  
• Ochsenbein, A. F., Pinschewer, D. D., Sierro, S., Horvath, E., Hengartner, H., Zinkernagel, R. M. (2000). Protective long-term antibody memory by antigen-driven and T help-dependent differentiation of long-lived memory B cells to short-lived plasma cells independent of secondary lymphoid organs. Proc. Natl. Acad. Sci. USA 97: 13263-13268 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS