LIGHT costimulates CD40 triggering and induces immunoglobulin secretion; a novel key partner in T cell‐dependent B cell terminal differentiation

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Abstract
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.