LIGHT costimulates CD40 triggering and induces immunoglobulin secretion; a novel key partner in T cell-dependent B cell terminal differentiation.
The T cell-dependent differentiation and function of B lymphocytes are tightly regulated by TNF ligands (L) and receptors interactions, such as CD40/CD40L, CD27/CD70 and CD134/CD314L. The LIGHT/HVEM system [homologous to lymphotoxin, inducible expression, competing for GpD of herpes virus, that binds to the herpes virus entry mediator (HVEM), and is expressed on activated T lymphocytes) focused our attention since HVEM has a large distribution that, in addition to T cells, DC or NK, includes tumor and normal B lymphocytes. HVEM was expressed on memory and naive B cells from peripheral blood or tonsils, but not on germinal center (GC) B cells. Costimulation by CD40L+LIGHT induced LIGHT expression at the B lymphocyte surface by a transcriptional mechanism since we detected de novo expression of LIGHT-specific mRNA. LIGHT expression was further enhanced by triggering of surface IgM, a stimulus that mimics a normal step of B cell physiology, i.e. specific antigen encounter. Stimulation by LIGHT increased the B cell proliferation induced by CD40L, and induced IgG and IgM (but not IgA) secretion. We conclude that LIGHT costimulation, that mimics the B cell encounter with activated LIGHT-expressing T lymphocytes, enhances both B cell proliferation and Ig production, and thus has a central importance for humoral immunity development.
Duhen
Thomas
T
Centre Lutte Contre le Cancer, Laboratoire d'Immunologie des Tumeurs, Université de la Méditerranée, Marseille, France.
Pasero
Christine
C
Mallet
Françoise
F
Barbarat
Bernadette
B
Olive
Daniel
D
Costello
Régis T
RT
D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology / Q000378:metabolism*; D023201:CD40 Ligand / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D019013:CD40 Antigens; D007136:Immunoglobulins; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand