Anti-CD40 antibody enhances responses to polysaccharide without mimicking T cell help.
Protection against infection with encapsulated bacteria is mediated by IgG antibodies against the capsular polysaccharides. Production of such antibodies is impaired during infancy, when susceptibility to bacterial meningitis is greatest. Recent studies have proposed the use of anti-CD40 antibody to increase responsivenesses to polysaccharide antigens. We show here that the IgG response to a model polysaccharide antigen is greatly increased, but retains thymus-independent characteristics--switching continues to be mainly to IgG3 and neither germinal centers nor memory B cells are formed. Furthermore, anti-CD40 causes striking splenomegaly in mice, which is accompanied by dramatic cellular redistribution and proliferation of dendritic cells, macrophages, T cells and endothelium, as well as B cells. These findings raise the possibility that the anti-CD40 effect is due mainly to increased activity of accessory cells that affect plasmablast growth and differentiation rather than mimicry of T cell help.
García de Vinuesa
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C
University of Birmingham/Medical Research Council Centre for Immune Regulation Birmingham, GB. c.g.vinuesa@bham.ac.uk
MacLennan
I C
IC
Holman
M
M
Klaus
G G
GG
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000955:Antigens, T-Independent / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D005362:Ficoll / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013997:Time Factors
D000906:Antibodies; D000955:Antigens, T-Independent; D019013:CD40 Antigens; D007074:Immunoglobulin G; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; D005362:Ficoll