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.
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18 December 2000
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December 18 2000
Virus-Induced Maturation and Activation of Autoreactive Memory B Cells
Amy J. Reed,
Amy J. Reed
aFrom The Wistar Institute, Philadelphia, Pennsylvania 19104
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Michael P. Riley,
Michael P. Riley
aFrom The Wistar Institute, Philadelphia, Pennsylvania 19104
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Andrew J. Caton
Andrew J. Caton
aFrom The Wistar Institute, Philadelphia, Pennsylvania 19104
Search for other works by this author on:
Amy J. Reed
aFrom The Wistar Institute, Philadelphia, Pennsylvania 19104
Michael P. Riley
aFrom The Wistar Institute, Philadelphia, Pennsylvania 19104
Andrew J. Caton
aFrom The Wistar Institute, Philadelphia, Pennsylvania 19104
Abbreviations used in this paper: AP, alkaline phosphatase; ASC, antibody-secreting cell; BCR, B cell receptor; ELISPOT, enzyme-linked immunospot; HA, hemagglutinin; HAU, hemagglutinating unit(s); HI, hemagglutination inhibition; HRP, horseradish peroxidase; PNA, peanut agglutinin; PR8, influenza virus A/PR/8/34; S1, site 1; tg, transgenic.
Received:
June 23 2000
Revision Requested:
September 18 2000
Accepted:
October 13 2000
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2000 The Rockefeller University Press
2000
The Rockefeller University Press
J Exp Med (2000) 192 (12): 1763–1774.
Article history
Received:
June 23 2000
Revision Requested:
September 18 2000
Accepted:
October 13 2000
Citation
Amy J. Reed, Michael P. Riley, Andrew J. Caton; Virus-Induced Maturation and Activation of Autoreactive Memory B Cells. J Exp Med 18 December 2000; 192 (12): 1763–1774. doi: https://doi.org/10.1084/jem.192.12.1763
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