Dynamics and magnitude of virus-induced polyclonal B cell activation mediated by BCR-independent presentation of viral antigen.
Hypergammaglobulinemia and production of autoantibodies occur during many viral infections, and studies have suggested that viral antigen-presenting B cells may become polyclonally activated by CD4 T cells in vivo in the absence of viral engagement of the BCR. However, we have reported that CD4 cells in lymphocytic choriomengitis virus (LCMV)-infected mice kill adoptively transferred B cells coated with LCMV class II peptides. We report here that most of the surviving naïve B cells presenting class II MHC peptides undergo an extensive differentiation process involving both proliferation and secretion of antibodies. Both events require CD4 cells and CD40/CD40L interactions but not MyD88-dependent signaling within the B cells. B cells taken from immunologically tolerant donor LCMV-carrier mice with high LCMV antigen load became activated following adoptive transfer into LCMV-infected hosts, suggesting that B cells present sufficient antigen for this process during a viral infection. No division or activation of B cells was detected at all in virus-infected hosts in the absence of cognate CD4 T cells and class II antigen. This approach, therefore, formally demonstrates and quantifies a virus-induced polyclonal proliferation and differentiation of B cells, which, due to their high proportion, would mostly have BCR not specific for the virus.
Jellison
Evan R
ER
Department of Pathology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Guay
Heath M
HM
Szomolanyi-Tsuda
Eva
E
Welsh
Raymond M
RM
D000595:Amino Acid Sequence; D000818:Animals; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002454:Cell Differentiation / Q000276:immunology; D002999:Clone Cells; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*
D000956:Antigens, Viral; D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell