The role of CD40-CD154 interaction in antiviral T cell-independent IgG responses.
Polyomavirus (PyV) infection elicits protective T cell-independent (TI) IgG responses in T cell-deficient mice. The question addressed in this report is whether CD40 signaling plays a role in this TI antiviral IgG response. Because CD40 ligand (CD40L) can be expressed on numerous cell types in addition to activated T cells, it is possible that cells other than T cells provide CD40L to signal through CD40 on B cells and hence positively influence the antiviral TI IgG responses. In this study we show, by blocking CD40-CD40L interactions in vivo with anti-CD40L Ab treatment in TCR betaxdelta-/- mice and by using SCID mice reconstituted with CD40-/- B cells, that the lack of CD40 signaling in B cells results in a 50% decrease in TI IgG secreted in response to PyV. SCID mice reconstituted with CD40L-/- B cells also responded to PyV infection with diminished IgG secretion compared with that of SCID mice reconstituted with wild-type B cells. This finding suggests that B cells may provide the CD40L for CD40 signaling in the absence of T cell help during acute virus infection. Our studies demonstrate that, although about half of the TI IgG responses to PyV are independent of CD40-CD40L interactions, these interactions occur in T cell-deficient mice and enhance antiviral TI Ab responses.
Szomolanyi-Tsuda
E
E
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA. Eva.Szomolanyi-Tsuda@umassmed.edu
Brien
J D
JD
Dorgan
J E
JE
Welsh
R M
RM
Garcea
R L
RL
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000955:Antigens, T-Independent / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D023201:CD40 Ligand; D002213:Capsid / Q000276:immunology; D036022:Capsid Proteins; D019674:Genes, T-Cell Receptor beta; D019676:Genes, T-Cell Receptor delta; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008024:Ligands; D008231:Lymphopenia / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D011120:Polyomavirus / Q000276:immunology*; D027601:Polyomavirus Infections / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D000955:Antigens, T-Independent; D019013:CD40 Antigens; D036022:Capsid Proteins; D007074:Immunoglobulin G; D008024:Ligands; D008562:Membrane Glycoproteins; C062481:VP1 protein, polyomavirus; D023201:CD40 Ligand