Murine cytomegalovirus infection-induced polyclonal B cell activation is independent of CD4+ T cells and CD40.
The results of this study demonstrate that murine cytomegalovirus (MCMV) induces polyclonal B cell activation in mice during the acute phase of primary infection. First flow cytometric analysis revealed that surface expression of CD45R, IgM, and IgK by splenocytes from MCMV-infected mice was significantly reduced with a concomitant increase in the frequency of surface IgG-expressing cells. Second, ELIspot assays demonstrated that the changes revealed by flow cytometry were paralleled by increases in the numbers of IgG-producing cells, especially those secreting IgG2a. Third, the IgG antibodies from MCMV-infected animals reacted against a variety of self and foreign antigens. MCMV-induced B cell activation was independent of CD4+ T-cell-mediated help and CD40, since activation was observed in two models of mice deficient for this T cell subset and in mice deficient for CD40. Reverse transcription-polymerase chain reaction analysis showed that mRNA transcripts for the cytokines IL-6, IL-10, and IFN-gamma were rapidly induced following infection with MCMV, but only IL-6 and IFN-gamma proteins were detectable by ELISA. In addition, the numbers of cells producing IL-6 and IFN-gamma were significantly increased in the spleen. The magnitude of the polyclonal B cell activation response was diminished by 50% in IL-6-deficient mice but not in mice lacking IFN-gamma. In the absence of IFN-gamma, surface expression and serum levels of IgG2a were reduced while IgG1 expression was increased.
Karupiah
G
G
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Sacks
T E
TE
Klinman
D M
DM
Fredrickson
T N
TN
Hartley
J W
JW
Chen
J H
JH
Morse
H C
HC
D016475:3T3 Cells; D000818:Animals; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007074:Immunoglobulin G / Q000032:analysis / Q000145:classification; D007371:Interferon-gamma / Q000172:deficiency / Q000502:physiology; D015850:Interleukin-6 / Q000172:deficiency; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008819:Mice, Nude; D018146:Muromegalovirus / Q000276:immunology*; D013045:Species Specificity; D013154:Spleen / Q000276:immunology / Q000473:pathology
D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D015850:Interleukin-6; D007371:Interferon-gamma