Virus-induced maturation and activation of autoreactive memory B cells.
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.
Reed
A J
AJ
Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Riley
M P
MP
Caton
A J
AJ
D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002999:Clone Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D007117:Immunization, Secondary; D007135:Immunoglobulin Variable Region / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D007150:Immunohistochemistry; D007156:Immunologic Memory / Q000276:immunology*; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D017421:Sequence Analysis
D001323:Autoantibodies; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007135:Immunoglobulin Variable Region