Virus-induced maturation and activation of autoreactive memory B cells

• Published in: The Journal of experimental medicine Vol. 192; no. 12; pp. 1763 - 1774
• Main Authors: Reed, A J, Riley, M P, Caton, A J
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 18.12.2000
• Subjects: Animals; Antibody Specificity; Autoantibodies - genetics; Autoantibodies - immunology; Autoimmunity - immunology; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; B-Lymphocytes - virology; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation; Clone Cells - cytology; Clone Cells - immunology; Clone Cells - metabolism; Clone Cells - virology; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Hybridomas - immunology; Immunization, Secondary; Immunoglobulin Variable Region - chemistry; Immunoglobulin Variable Region - genetics; Immunoglobulin Variable Region - immunology; Immunohistochemistry; Immunologic Memory - immunology; influenza A virus; Influenza A virus - genetics; Influenza A virus - immunology; Lymph Nodes - cytology; Lymph Nodes - immunology; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Transgenic; Mutation - genetics; Original; Sequence Analysis
• ISSN: 0022-1007; 1540-9538; 1892-1007
• DOI: 10.1084/jem.192.12.1763

We have examined B cell populations that participate in distinct phases of the immune response to the influenza virus A/PR/8/34 hemagglutinin (HA) for their susceptibility to negative selection in mice that express the HA as a neo-self-antigen (HA104 mice). We demonstrated previously that specificity for the neo-self-HA causes a population of immunoglobulin G antibody-secreting cells, which dominate the primary response to virus immunization in BALB/c mice, to be negatively selected in HA104 mice. We find here that in contrast to these primary response B cells, HA-specific memory response B cells developed equivalently in HA104 and nontransgenic (BALB/c) mice. Indeed, there was no indication that HA-specific B cells were negatively selected during memory formation in influenza virus-immunized HA104 mice, even though the neo-self-HA can be recognized by memory B cells. Furthermore, HA-specific autoantibodies were induced in the absence of virus immunization by mating HA104 mice with mice transgenic for a CD4(+) HA-specific T cell receptor. These findings indicate that specificity for a self-antigen does not prevent the maturation of autoreactive B cells in the germinal center pathway. Rather, the availability of CD4(+) T cell help may play a crucial role in regulating autoantibody responses to the HA in HA104 mice.