Induction of long-lived germinal centers associated with persisting antigen after viral infection.
Vesicular stomatitis virus (VSV) induces an early T cell-independent neutralizing lgM response that is followed by a long-lived, T cell-dependent lgG response. We used the specific amplification factor of several 100x of VSV-virions for immunohistology to analyze the localization of VSV-specific B cells at different time points after immunization. At the peak of the IgM response (day 4), VSV-specific B cells were predominantly present in the red pulp and marginal zone but not in the T area. These B cells were mostly stained in the cytoplasm, characterizing them as antibody secreting cells. By day 6 after immunization, germinal centers (GC) containing surface-stained VSV-specific B cells became detectable and were fully established by day 12. At the same time, large VSV-specific B cell aggregates were present in the red pulp. High numbers of VSV-specific GC associated with persisting antigen were present 1 mo after immunization and later, i.e., considerably longer than has been observed for haptens. Some GC, exhibiting follicular dendritic cells and containing VSV-specific, proliferating B cells were still detectable up to 100 d after immunization. Long-lived GC were also observed after immunization with recombinant VSV-glycoprotein in absence of adjuvants. Thus some anti-virally protective (memory) B cells are cycling and locally proliferate in long-lived GC in association with persisting antigen and therefore seem responsible for long-term maintenance of elevated antibody levels. These observations extend earlier studies with carrier hapten antigens in adjuvant depots or complexed with specific IgG; they are the first to show colocalization of antigen and specific memory B cells and to analyze a protective neutralizing antibody response against an acute viral infection.
Bachmann
M F
MF
Department of Pathology, University of Zürich, Switzerland.
Odermatt
B
B
Hengartner
H
H
Zinkernagel
R M
RM
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D006224:Cricetinae; D004797:Enzyme-Linked Immunosorbent Assay; D018858:Germinal Center / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007668:Kidney; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000276:immunology; D018353:Rhabdoviridae Infections / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology; D018411:Spodoptera; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014162:Transfection; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology / Q000302:isolation & purification
D000914:Antibodies, Viral; D000956:Antigens, Viral; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011994:Recombinant Proteins